<![CDATA[Tuberculosis]]> https://www.eurekaselect.com RSS Feed for Disease Wise Article | BenthamScience EurekaSelect (+http://eurekaselect.com) Fri, 29 Mar 2024 13:17:49 +0000 <![CDATA[Tuberculosis]]> https://www.eurekaselect.com https://www.eurekaselect.com <![CDATA[TLC Bioautography on Screening of Bioactive Natural Products: An Update Review]]>https://www.eurekaselect.comarticle/95417Background: TLC bioautography is a hyphenated technique combining planar chromatographic separation and in situ biological activity detection. This coupled method has been receiving much attention in screening bio-active natural products because of its properties of being simple, rapid, inexpensive, and effective.

Methods: The recent progress in the development of method of TLC bioautography for detecting antimicrobial and enzyme inhibitory activities dating between 2012 and early 2018 has been reviewed. The applications of this method in biological screening of natural products were also presented.

Results: Some anaerobic and microaerophilic bacteria and a causative bacterium of tuberculosis have been adopted to TLC direct bioautography. Seven types of enzymes including acetylcholinesterase, glucosidase, lipase, xanthine oxidase, tyrosinase, monoamine oxidase, and dipeptidyl peptidase IV have so far been adopted on TLC bioautography. Its new application in screening antiurolithiatic agents was included.

Conclusion: The standard experimental procedures are required for TLC antioxidant and antimicrobial assays. Some new enzymes should be attempted and adopted on TLC bioautography. The existing TLC methods for enzyme inhibition need more application studies to assess their screening capacity in the discovery of active compounds. The GC-MS or LC-MS approaches have gradually been coupled to TLC bioautography for fast structural characterization of active compounds.

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<![CDATA[Potential Drug Targets in Mycobacterial Cell Wall: Non-Lipid Perspective]]>https://www.eurekaselect.comarticle/90936 <![CDATA[DESIGN, <i>In silico</i> Modeling, Toxicity study and Synthesis of Novel Substituted Semicarbazide Derivatives of Pyrimidine: An Antitubercular Agent]]>https://www.eurekaselect.comarticle/93311Background: A series of 1-(2-(2-amino-5-carbamoyl-6-(1-(substitutedphenyl) prop-1-enyl) pyrimidin-4-yloxy)acetyl) semicarbazide (4a-i) derivatives was synthesized from substituted aromatic aldehydes, ethyl cyanoacetate and guanidine hydrochloride and characterized by analytical and spectral data, FTIR, 1H-NMR and Mass spectroscopy data.

Methods: The antiTB action of the synthesized compounds was screened in comparison with the standard drug Rifampicin using MABA assay method. The SAR of substituted aromatic aldehydes with modification at ortho, meta and para positions with electron withdrawing group.

Result: The compounds 1-(2-(2-amino-5- carbamoyl-6-(1-(2-fluorophenyl) prop-1-enyl) pyrimidin-4- yloxy) acetyl) semicarbazide and 1-(2-(2-amino- 5-carbamoyl-6-(1-(3-chlorophenyl) prop-1-enyl) pyrimidin-4-yloxy) acetyl) semicarbazide showed equal MIC values against Mycobacterium tuberculosis H37Ra with the value of 3.90μg/ml.

Conclusion: The SAR study revealed that the antiTB activity of the synthesized compounds were affected by lipophilicity of the substituent.

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<![CDATA[Defining ‘Satisfactory Response’ to Therapy in Abdominal Tuberculosis: A Work in Progress]]>https://www.eurekaselect.comarticle/93858 <![CDATA[Current Discovery Progress of Some Emerging Anti-infective Chalcones: Highlights from 2016 to 2017]]>https://www.eurekaselect.comarticle/91869 <![CDATA[Synthesis, Antitubercular Activity, Molecular Modeling and Docking Studies of Novel Thiazolidin-4-One Linked Dinitrobenzamide Derivatives]]>https://www.eurekaselect.comarticle/91859Background: Tuberculosis is a catastrophe sprawled across the world. The World Health Organization Global Tuberculosis Report 2017 inferred that there were an estimated 10.4 million people suffered from tuberculosis including 490000 Multidrug-Resistant TB (MDR-TB) cases. Several new lead molecules like dinitrobenzamide derivatives were found to be highly active against multidrugresistant strains of M. tuberculosis. To further explore the pharmacophoric space around the dinitobenzamide moiety, a series of compounds have been synthesized by linking it with the thiazolidin- 4-one. The presented work is an effort to study the biological effect of thiazolidin-4-one scaffold on dinitrobenzamide derivatives as antitubercular agents. A molecular modeling study was also performed on the synthesized molecules to reveal the requirements for further lead optimization.

Methods: The thiazolidin-4-one linked 3,5-dinitrobenzamide derivatives have been synthesized by onepot three-component condensation reaction of an amine, substituted aldehydes and thioglycolic acid in presence of N, N'-Dicyclohexylcarbodiimide (DCC). These compounds were evaluated against Mycobacterium tuberculosis H37Ra. A pharmacophore modeling approach has been used in order to explore the collection of possible pharmacophore queries of thiazolidin-4-one linked 3, 5-dinitrobenzamide derivatives against M. tuberculosis. The synthesized compounds were docked on to the M. tuberculosis DprE1 enzyme to identify the structural features requirement of these analogs against this potential target of M. tuberculosis.

Results: The synthesized compounds showed the antitubercular activity in the range of 6.25-50 μg/ml. The pharmacophore modeling suggests that the presence of aromatic moiety, thiazolidin-4-one ring and one of the nitro groups are significant for inhibiting the enzymatic activity. While docking studies showed that hydrophobic and hydrogen bond interactions of the aromatic moiety and nitro group crucial to inactivate the DprE1 enzyme.

Conclusion: The study showed that the linking of thiazolidin-4-one with dinitrobenzamide leads to compounds active against M. tuberculosis. These findings also suggested that further lead optimization would be carried out by focusing on the aromatic system along with electron-rich substituents placed on the thiazolidin-4-one for making better hydrophobic and hydrogen bond interactions with the DprE1 target.

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<![CDATA[Synthesis and In vitro Antibacterial, Antitubercular Studies of Novel Fluoroquinolones Analogs Containing 4-substituted Sec Amine]]>https://www.eurekaselect.comarticle/90757Background: Tuberculosis is a contagious, air borne disease and second leading cause of death among infectious diseases worldwide. Fluoroquinolones are well-known antibacterial agents and they were recommended as second-line of antitubercular drugs.

Method: A series of novel fluoroquinolone analogs 6-24 was effectively synthesized. An attempt was made by tagging the substituted pyrazole on to fluoroquinolones for the first time at C-7 position. The newly synthesized compounds were characterized by FTIR, 1HNMR, ESI-MS, HR-MS and elemental analysis. The in vitro antibacterial activity of all the title compounds was investigated against various gram positive, gram negative bacterial organisms and in vitro antitubercular activity against Mycobacterium Tuberculosis H37Rv strain.

Result: Most of the synthesized compounds showed comparable activity against the entire gram positive and gram negative bacterial organisms. Fluoroquinolone 16 showed enhanced activity against both type of bacterial strains and compound 11showed promising activity against MTB-H37Rv strain.

Conclusion: Some of the novel fluoroquinolone analogs (11, 16) showed potent antibacterial, antitubercular activity.

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<![CDATA[Distribution and Characteristics of Intrathoracic Lymphadenopathy in TB/HIV Co-Infection]]>https://www.eurekaselect.comarticle/93708Background: Intrathoracic Lymphadenopathy (ITLN) in Human Immunodeficiency Virus (HIV) infected patients may have various etiologies and prognoses. Etiologies of ITLN can be distinguished based on the distribution of enlarged lymph nodes. Sometimes tuberculosis (TB) is the first sign of underlying HIV infection.

Objectives: We sought to determine ITLN distribution and associated pulmonary findings in TB/HIV co-infection using Computed Tomography (CT) scan.

Methods: In this retrospective, observational, cross-sectional study, chest CT scans of 52 patients with TB/HIV co-infection were assessed for enlarged intrathoracic lymph nodes (>10 mm in short axis diameter), lymphadenopathy (LAP) distribution, calcification, conglomeration, the presence of hypodense center and associated pulmonary abnormalities. LAP distribution was compared in TB/HIV co-infection with isolated TB infection.

Results: Mediastinal and/or hilar LAP were seen in 53.8% of TB/HIV co-infection patients. In all cases, LAP was multistational. The most frequent stations were right lower paratracheal and subcarinal stations. Lymph node conglomeration, hypodense center and calcification were noted in 25%, 21.4% and 3.5% of patients, respectively. LAP distribution was the same as that in patients with isolated TB infection except for the right hilar, right upper paratracheal and prevascular stations. All patients with mediastinal and/or hilar adenopathy had associated pulmonary abnormalities.

Conclusion: All patients with TB/HIV co-infection and mediastinal and/or hilar adenopathy had associated pulmonary abnormalities. Superior mediastinal lymph nodes were less commonly affected in TB/HIV co-infection than isolated TB.

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<![CDATA[Preparation and Antitubercular Activities of Palindromic Hydrazinecarbothioamides and Carbonothioic Dihydrazides]]>https://www.eurekaselect.comarticle/91980Background: With approximately one-third of the world’s population infected, tuberculosis continues to be a global public health crisis. The rise of strains that are unusually virulent or highly resistant to current drugs is a cause of special concern, prompting research into new classes of compounds, as well as the re-evaluation of known chemotherapeutic agents.

Objectives: The antimycobacterial activities associated with some recently-reported thiocarbonyl compounds kindled our interest in the synthesis of substituted hydrazinecarbothioamides (3) and carbonothioic dihydrazides (4), with the aim of investigating their potential in antitubercular drug design and discovery.

Methods: In the present study, the title compounds 3 and 4 were prepared by the condensation of hydrazines with isothiocyanates in reactions readily controlled by stoichiometry, temperature and solvent. The compounds were assessed against Mycobacterium bovis BCG in Kirby-Bauer disc diffusion, and minimum inhibitory concentrations were determined against the virulent strain M. tuberculosis Erdman.

Results: The chemical structures of these thermally stable compounds were determined by IR, 1HNMR, 13C-NMR, high-resolution mass spectrometry and elemental analysis. In the Kirby-Bauer disc diffusion assay, some of the compounds showed substantial diameters of inhibition against BCG. In some cases, the zones of inhibition were so large that no growth at all was observed on the assay plates. Against M. tuberculosis Erdman, several of the compounds showed significant activities. Compound 3h was the most active, demonstrating a minimum inhibitory concentration of 0.5 µg/mL.

Conclusion: We found that the title compounds may be prepared conveniently in excellent purity and good yields. They are readily identified on the basis of their characteristic spectra. Some members of this class showed significant activities against mycobacteria. We conclude that further work will be warranted in exploring the antitubercular properties of these compounds.

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<![CDATA[Potential Triazole-based Molecules for the Treatment of Neglected Diseases]]>https://www.eurekaselect.comarticle/85022 <![CDATA[Privileged Structures in the Design of Potential Drug Candidates for Neglected Diseases]]>https://www.eurekaselect.comarticle/86487Background: Privileged motifs are recurring in a wide range of biologically active compounds that reach different pharmaceutical targets and pathways and could represent a suitable start point to access potential candidates in the neglected diseases field. The current therapies to treat these diseases are based in drugs that lack of the desired effectiveness, affordable methods of synthesis and allow a way to emergence of resistant strains. Due the lack of financial return, only few pharmaceutical companies have been investing in research for new therapeutics for neglected diseases (ND).

Methods: Based on the literature search from 2002 to 2016, we discuss how six privileged motifs, focusing phthalimide, isatin, indole, thiosemicarbazone, thiazole, and thiazolidinone are particularly recurrent in compounds active against some of neglected diseases.

Results: It was observed that attention was paid particularly for Chagas disease, malaria, tuberculosis, schistosomiasis, leishmaniasis, dengue, African sleeping sickness (Human African Trypanosomiasis - HAT) and toxoplasmosis. It was possible to verify that, among the ND, antitrypanosomal and antiplasmodial activities were between the most searched. Besides, thiosemicarbazone moiety seems to be the most versatile and frequently explored scaffold. As well, phthalimide, isatin, thiazole, and thiazolidone nucleus have been also explored in the ND field.

Conclusion: Some described compounds, appear to be promising drug candidates, while others could represent a valuable inspiration in the research for new lead compounds.

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<![CDATA[Social Determinants Associated with Tuberculosis Mortality in a General Hospital in Mexico ]]>https://www.eurekaselect.comarticle/95949Background: Most TB deaths can be prevented with timely diagnosis and appropriate treatment. In fact, millions of people are diagnosed and treated successfully every year, avoiding millions of deaths. However, globally, there are still huge gaps in detection and treatment.

Objective: To identify the social determinants associated with mortality due to TB in a general hospital in Mexico.

Methodology: All patients admitted with a diagnosis of pulmonary tuberculosis to the Emergency Department of a hospital in Mexico were included during a 10-month period. At the end of the study, the condition of discharge of all cases was obtained from the electronic database of the State Tuberculosis Program.

Results: One-hundred and twenty-four patients with tuberculosis were included in the sample. Thirty-eight patients (30.6%) died during their hospital stay and eleven (8.9%) died outside the hospital after their discharge, for a total of 49 (39.5%) deaths. Of the 29 patients with HIV/AIDS, 12 died (41.3%). Logistic regression analysis showed that older age, imprisonment, and previous tuberculosis were significant predictors of mortality.

Conclusion: The mortality of tuberculosis patients diagnosed in HGT is very high, mainly because the diagnosis is established at the hospital level, which implies a late diagnosis.

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<![CDATA[Novel Benzylidenehydrazide-1,2,3-Triazole Conjugates as Antitubercular Agents: Synthesis and Molecular Docking]]>https://www.eurekaselect.comarticle/91794Background & Objective: Novel 1,2,3-triazole based benzylidenehydrazide derivatives were synthesized and evaluated for antitubercular activity against Mycobacterium tuberculosis (MTB) H37Ra, M. bovis BCG and cytotoxic activity. Most of the derivatives exhibited promising in vitro potency against MTB characterized by lower MIC values.

Methods: Among all the synthesized derivatives, compound 6a and 6j were the most active against active and dormant MTB H37Ra, respectively. Compound 6d was significantly active against dormant and active M. bovis BCG.

Results: The structure activity relationship has been explored on the basis of anti-tubercular activity data. The active compounds were also tested against THP-1, A549 and Panc-1 cell lines and showed no significant cytotoxicity. Further, the synthesized compounds were found to have potential antioxidant with IC50 range = 11.19-56.64 µg/mL. The molecular docking study of synthesized compounds was performed against DprE1 enzyme of MTB to understand the binding interactions.

Conclusion: Furthermore, synthesized compounds were also analysed for ADME properties and the potency of compounds indicated that, this series can be considered as a starting point for the developement of novel and more potent anti-tubercular agents in future.

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<![CDATA[Green Synthesis of Gold Nanoparticles Using Different Leaf Extracts of Ocimum gratissimum Linn for Anti-tubercular Activity]]>https://www.eurekaselect.comarticle/92228Background: Tuberculosis is a greatest threat to human health. It requires urgent need to seek new devise alternate strategies and ant-tubercular compounds. In the present scenario, Nonmaterias, have opened new avenues in medicine, diagnosis and therapeutics.

Objective: In view of this, the current study aims to synthesize gold nanoparticles and determine its efficacy to inhibit Mycobacterium tuberculosis.

Methods: Gold nanoparticles (GNPs) synthesized from medicinal plant, such as Ocimum gratissimum linn, were tested against Mycobacterium tuberculosis (H37RV strain). Gold nanoparticles were characterized by UV-Vis spectrophotometer, FTIR, SEM and TEM. TEM results revealed that the GNPs were found spherical in structure and around 10-25 nm in diameter. UV-Vis spectroscopy exhibited an absorption peak at 348 nm. Fourier transform infra-red spectroscopy showed the GNPs have coated with phytoconstituents (terpenoids) that indicate the role of bio-molecules responsible for efficient stabilization and capping of the gold nanoparticles. In vitro model was designed to determine minimum inhibitory concentration (MIC) of each sample by Lowenstein Jensen (LJ) slope method.

Results: The results showed that the presence of ursolic acid in ethanolic and hydroalcoholic extracts was found to be 2.89% and 1.97%, respectively. GNPs of ethanolic and hydroalcoholic exhibited anti-tubercular activity, with MIC 2.5 µg/ml and 20 µg/ml, respectively. While ethanolic and hydroalcoholic extracts showed such activity at concentrations 50 µg/ml and 75 µg/ml, respectively.

Conclusion: GNPs synthesized from ethanolic extract showed profound efficiency to kill mycobacteria. As in this method no chemical reagents were used, the synthesized gold nanoparticles have potential for biological applications. There is an urgent need to further development of nano-antibiotic for tuberculosis.

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<![CDATA[Synthesis and Biological Activity of 2-Amino- and 2-aryl (Heteryl) Substituted 1,3-Benzothiazin-4-ones]]>https://www.eurekaselect.comarticle/93694 <![CDATA[Impact of Diabetes Mellitus on Radiological Presentation of Pulmonary Tuberculosis in Otherwise Non-Immunocompromised Patients: A Systematic Review]]>https://www.eurekaselect.comarticle/92194Background: Studies on the influence of diabetes mellitus on the radiological presentation of pulmonary tuberculosis performed so far yielded inconsistent results. We aimed to summarize the relevant evidence on this topic systematically.

Methods: We systematically searched PubMed/MEDLINE (1980–2016) and the references of related articles (English-language reports) for observational studies that compared the radiological presentation of pulmonary tuberculosis in diabetes and non-diabetes patients.

Results: A total of fifteen studies that enrolled 2,020 diabetic patients and 5,280 controls were included in this systematic review. None of the included studies showed any significant difference in the upper lobe involvement and or in bilateral disease between diabetes and non-diabetes patients. However, lower lung field cavitary disease was found to be more frequent (relative risks ranging from 2.76, 95% CI 2.28-3.35 to 4.47, 95% CI 2.62-7.62) in patients with poor glycemic control (HbA1C >9%). Similarly, a significantly higher proportion of cavitary disease in diabetes patients was reported by 7 out of 15 studies, the meta-analysis of cavities of any size/site also showed the significantly higher risk of cavitary disease in diabetes patients (p-value = 0.0008). Three studies stratified the presence of cavities by diabetes control status, finding a higher proportion of cavities in uncontrolled diabetic patients (relative risks ranging from 1.85, 95%CI 1.34-2.55 to 3.59, 95%CI 2.53-5.11). One out of four studies found a significantly higher proportion of nodular infiltrations in diabetes versus non-diabetes patients.

Conclusion: While there is no difference in localization of lung lesions between patients with diabetes and non-diabetes, our review found that the risk of cavitary disease is relatively higher in diabetes patients. It is essential for researchers to unify the criteria for diabetes diagnosis, patient selection, and radiographic severity and stratify the results by the potentially confounding factors.

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<![CDATA[Biopolymer Catalysed Synthesis of 6-methyl-4-phenylcarbamoyl-1, 2, 3, 4- Tetrahydropyrimidine-2-ones and Evaluation of their Anti-bacterial and Anti-tubercular Activities]]>https://www.eurekaselect.comarticle/90174Background: An efficient one-pot biocatalysed ultrasound assisted synthesis of dihydropyrimidinones/ thiones has been developed under solvent free conditions.

Materials and Methods: The use of biodegradable, non toxic, agar-powder as a catalyst provide advantages like high yield, simple operation, mild reaction condition with short reaction time. 1,2,3,4- tetrahydropyrimidine-2-ones/thiones formed were characterized by mass and 1H NMR spectroscopy.

Results: The dihydropyrimidinones substituted with electron donating groups like fluorine, hydroxy along with thienyl groups exhibited good antibacterial activity. The compounds exhibited favorable binding interactions with mycobacterium target protein H37Rv.

Conclusion: 4-methoxy substituted dihydropyrimidinones derivative showed significant antituberculosis activity.

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<![CDATA[Trends in Diagnosis for Active Tuberculosis Using Nanomaterials]]>https://www.eurekaselect.comarticle/92988Background: Tuberculosis (TB), one of the leading causes of death worldwide, is difficult to diagnose based only on signs and symptoms. Methods for TB detection are continuously being researched to design novel effective clinical tools for the diagnosis of TB.

Objective: This article reviews the methods to diagnose TB at the latent and active stages and to recognize prospective TB diagnostic methods based on nanomaterials.

Methods: The current methods for TB diagnosis were reviewed by evaluating their advantages and disadvantages. Furthermore, the trends in TB detection using nanomaterials were discussed regarding their performance capacity for clinical diagnostic applications.

Results: Current methods such as microscopy, culture, and tuberculin skin test are still being employed to diagnose TB, however, a highly sensitive point of care tool without false results is still needed. The utilization of nanomaterials to detect the specific TB biomarkers with high sensitivity and specificity can provide a possible strategy to rapidly diagnose TB. Although it is challenging for nanodiagnostic platforms to be assessed in clinical trials, active TB diagnosis using nanomaterials is highly expected to achieve clinical significance for regular application. In addition, aspects and future directions in developing the high-efficiency tools to diagnose active TB using advanced nanomaterials are expounded.

Conclusion: This review suggests that nanomaterials have high potential as rapid, costeffective tools to enhance the diagnostic sensitivity and specificity for the accurate diagnosis, treatment, and prevention of TB. Hence, portable nanobiosensors can be alternative effective tests to be exploited globally after clinical trial execution.

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<![CDATA[Design, Synthesis and Anti-tuberculosis Activity of Hydrazones and N-acylhydrazones Containing Vitamin B6 and Different Heteroaromatic Nucleus]]>https://www.eurekaselect.comarticle/91299Background: The term vitamin B6 refers to a set of six compounds, pyridoxine,pyridoxal ,and pyridoxamine and their phosphorylated forms, among which pyridoxal 5´-phosphate (PLP) is the most important and active form acting as a critical cofactor. These compounds are very useful in medicinal chemistry because of their structure and functionalities and are also used in bioinorganic chemistry as ligands for complexation with metals.

Methods: In this study, a series of hydrazones 1a-g and N-acylhydrazones 2a-f containing vitamin B6 have been synthesized from commercial pyridoxal hydrochloride and the appropriate aromatic or heteroaromatic hydrazine or N-acylhydrazine. All synthesized compounds have been fully characterized and tested against Mycobacterium tuberculosis.

Results: Among the N-acylhydrazones derivatives 2a-f, 2d (para- pyridine substituted Nacylhydrazone; MIC = 10.90 µM) exhibited the best activity. The ortho-pyridine derivative 2b exhibited intermediate activity (MIC = 87.32 µM), and the meta-pyridine derivative 2c was inactive. In case of the hydrazone series 1a-g, 7-chloroquinoxaline derivative 1f (MIC = 72.72 µM) showed the best result, indicating that the number of nitrogen and chlorine atoms in the radical moiety play an important role in the anti-tuberculosis activity of the quinoxaline derivatives (1f and 1g).

Conclusion: The data reported herein indicates that the isoniazid derivative 2d (MIC = 10.90 µM) exhibited the best activity in the N-acylhydrazone series and; the quinoxaline nucleus derivative 1f (MIC = 72.72 µM) was the most active compound in the hydrazone series.

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<![CDATA[Tuberculous Tenosynovitis of the Wrist: A Report of Two Cases with Special Reference to Magnetic Resonance Findings]]>https://www.eurekaselect.comarticle/93151Background: Tuberculous tenosynovitis of the wrist is rare among cases of musculoskeletal tuberculosis. It is a slow, progressive disease with silent symptoms, leading to a late diagnosis. Also, it can be misdiagnosed as inflammatory arthritis, pyogenic infections, and inflammatory tenosynovitis. Thus, patients present with destructive changes of the bone and joint, as well as abscesses, often receive incorrect or unnecessary medical and surgical treatment.

Discussion: Well-documented anamneses along with physical examinations and radiologic imaging methods, such as computed tomography (CT) and magnetic resonance imaging (MRI), can be useful in the diagnosis of tuberculous tenosynovitis. All chronic synovitis of the wrist with longstanding pain should be considered as mycobacterial infection and an important differential diagnosis. Early diagnosis followed by extensive debridement and antituberculous chemotherapy provides good functional results.

Conclusion: This article presents the cases of two patients with wrist tuberculous tenosynovitis and the respective MRI findings. It also includes a literature review.

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<![CDATA[Clinical Management of Drug-resistant Mycobacterium tuberculosis Strains: Pathogen-targeted Versus Host-directed Treatment Approaches]]>https://www.eurekaselect.comarticle/92072Background: Despite exerted efforts to control and treat Mycobacterium tuberculosis (MTB) strains, Tuberculosis (TB) remains a public health menace. The emergence of complex drug-resistant profiles, such as multi-drug resistant and extensively drug-resistant MTB strains, emphasizes the need for early diagnosis of resistant cases, shorter treatment options, and effective medical interventions.

Objective: Solutions for better clinical management of drug-resistant cases are either pathogencentered (novel chemotherapy agents) or host-directed approaches (modulating host immune response to prevent MTB invasion and pathogenesis).

Results: Despite the overall potentiality of several chemotherapy agents, it is feared that their effectiveness could be challenged by sequential pathogen adaptation tactics. On the contrary, host-directed therapy options might offer a long-term conceivable solution.

Conclusion: This review discusses the main suggestions proposed so far to resolve the clinical challenges associated with drug resistance, in the context of TB. These suggestions include novel drug delivery approaches that could optimize treatment outcome and increase patients’ compliance to the treatment.

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<![CDATA[Targeting DNA Repair Systems in Antitubercular Drug Development]]>https://www.eurekaselect.comarticle/88234 <![CDATA[Evaluation of the QuantiFERON®-TB Gold In-Tube Assay and Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in an Iranian Referral Hospital]]>https://www.eurekaselect.comarticle/88871Background: Mycobacterium tuberculosis remains as a vital threat to global health and its diagnosis is still complicated. Since there is no gold standard for the diagnosis of latent tuberculosis infection (LTBI), its diagnosis routinely relies on measurement of host immune responses to M. tuberculosis antigens using the Tuberculin Skin Test (TST) and Interferon-Y Release Assays (IGRAs).

Objective: The aim of this study was to evaluate LTBI among hospitalized children and their parents/ guardians as general populations.

Methods: A cross-sectional study comparing TST and IGRA for the diagnosis of suspected LTBI was performed in children and their guardians (as general population) in Children Medical Center, an Iranian referral hospital.

Results: In this study, 81 patients hospitalized in CMC and 102 patient's guardians were included. A total of 57 patients (70.4%) had performed a TST and were interpreted during the study. Among them, 32 (56%) had a positive test result when a cut-off of 10 mm induration. There were fewer positive IGRA test results than positive TST results (33% versus 56%) in children. Among guardians, TST and IGRA were positive in 41% and 40% respectively. The agreement between the IGRA test and the TST among them was 0.7, while this was as slightly lower in children (0.63).

Conclusion: The results of our study indicate that the IGRA test has a higher specificity than TST, especially in children, while the frequency of positive results with both tests in adults was similar. Considering the false positive results reported with the TST, replacement of the IGRA test with TST in children is recommended.

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<![CDATA[Prevalence of Tuberculosis in a Prison in Tehran by Active Case Finding]]>https://www.eurekaselect.comarticle/90223Background: Tuberculosis [TB] is one of the most important infectious diseases among prisoners. TB Screening plays an important role in prevention among prisoners and their visitors, also better caring of the patients. Active case finding is one of screening methods that is relatively an easy one to find TB suspected prisoners. Therefore, we aimed to assess the prevalence of TB in male prisoners in Tehran, Iran.

Methods: This study was conducted among male prisoners in Great Tehran Prison to screen and diagnose TB patients from October 2013 to May 2014. We used active case finding [ACF] as a screening method to find TB suspected prisoners in which healthcare staff explained TB symptoms for prisoners and individuals with those symptoms referred to the clinic for further work up (sputum sample tests).

Results: In total of 6900 prisoners, 448 (6.5%) prisoners were TB suspected by ACF and only nine patients were diagnosed with tuberculosis, indicating the prevalence of 0.13%.

Conclusion: The relatively low TB prevalence within prisoners besides considering likely common symptoms in ACF may result in many false positive cases during screening (6.5% vs. 0.13%). But, ACF is more fast, easy and affordable method to find TB suspected prisoners. Also, during this active method, prisoners are trained about TB symptoms so, it has a more prolonged effect towards screening goals.

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<![CDATA[Surreptitious TB Infections with Recently Identified DM People: A Cross- Sectional Study]]>https://www.eurekaselect.comarticle/93628Background: Tuberculosis (TB) among Diabetes Mellitus (DM) population is more expected to fail treatment of TB due to smear-negative TB.

Objective: We sought to compare and evaluate different methods to study the frequency of TB infections among DM patients.

Methods: Blood, sputum and urine samples were collected from 500 newly identified diabetic patients from different diabetic clinics in Warangal districts. Smear microscopy, Culture and Line Probe Assay by Polymerase Chain Reaction (LPA PCR) were used for identification of tuberculosis.

Results: Based on the chest X-Ray of 200 diabetic patients, suspected with pulmonary infections, 113 were males, 85 were females and 2 were children. All 200 patients were tested for tuberculosis infections, 55 were confirmed based on chest X-ray lesions. Off 55 patients, 30 were positive and 25 were negative for AFB microscopy, but were shown positive for chest X-ray. 22 were reported to be culture positive on solid media and identified as Mycobacterium tuberculosis based on morphology and biochemical methods. 36 samples were identified to be positive for LED, FM microscopy and LPA. Off 36 positive samples, 2 were MDR-TB and 34 were MTB based on LPA PCR method. Off 25 smear negative samples, 2 were identified as culture positive and confirmed to be MTB by morphological, biochemical tests.

Conclusion: Smear Negative Microscopy plays a vital role in the spread of tuberculosis infection among diabetic patients. Along with the smear microscopy, there is a need to rely on other methods for rapid identification and diagnosis of tuberculosis among the diabetic patients to control the spread of infection in the community and household contacts.

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<![CDATA[Synthesis and Structural Elucidation of Novel Benzothiazole Derivatives as Anti-tubercular Agents: In-silico Screening for Possible Target Identification]]>https://www.eurekaselect.comarticle/91455Background: Benzothiazole derivatives are known for anti-TB properties. Based on the known anti-TB benzothiazole pharmacophore, in the present study, we described the synthesis, structural elucidation, and anti-tubercular screening of a series of novel benzothiazole (BNTZ) derivatives (BNTZ 1–7 and BNTZ 8–13).

Objective: The study aims to carry out the development of benzothiazole based anti-TB compounds.

Methods: Title compounds are synthesized by microwave method and purified by column chromatography. Characterization of the compounds is achieved by FT-IR, NMR (1H and 13C), LCMS and elemental analysis. Screening of test compounds for anti-TB activity is achieved by Resazurin Microplate Assay (REMA) Plate method.

Results: It was noted that the BNTZ compound with an isoquinoline nucleus (BNTZ 9) exhibited remarkable anti-tubercular activity at 8 µg/mL against both the susceptible strain H37Rv and the multi-drug resistant tuberculosis strains of Mycobacterium tuberculosis. On the other hand, the BNTZ compound with a naphthalene nucleus (BNTZ 2) revealed anti-tubercular activity at 6 µg/mL and 11 µg/mL against both the susceptible strain H37Rv and the multi-drug resistant tuberculosis strains of M. tuberculosis, respectively. One of the selected BNTZ derivatives BNTZ 13 was used for single crystal X-ray studies.

Conclusion: To identify the appropriate target for potent BNTZ compounds from the series, molecular modeling studies revealed the multiple strong binding of several BNTZs with mycobacterium lysine-ɛ-aminotransferase and decaprenyl-phosphoryl-β-D-ribose 2'-oxidase. The interaction is derived by forming favorable hydrogen bonds and stacking interactions. This new class of BNTZ compounds gave promising anti-tubercular actions in the low micromolar range, and can be further optimized on a structural basis to develop promising, novel, BNTZ pharmacophore-based anti-tubercular drugs.

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<![CDATA[Does the Development of Vaccines Advance Solutions for Tuberculosis?]]>https://www.eurekaselect.comarticle/94790Background: Mycobacterium tuberculosis (Mtb) is considered as one of the most efficacious human pathogens. The global mortality rate of TB stands at approximately 2 million, while about 8 to 10 million active new cases are documented yearly. It is, therefore, a priority to develop vaccines that will prevent active TB. The vaccines currently used for the management of TB can only proffer a certain level of protection against meningitis, TB, and other forms of disseminated TB in children; however, their effectiveness against pulmonary TB varies and cannot provide life-long protective immunity. Based on these reasons, more efforts are channeled towards the development of new TB vaccines. During the development of TB vaccines, a major challenge has always been the lack of diversity in both the antigens contained in TB vaccines and the immune responses of the TB sufferers. Current efforts are channeled on widening both the range of antigens selection and the range of immune response elicited by the vaccines. The past two decades witnessed a significant progress in the development of TB vaccines; some of the discovered TB vaccines have recently even completed the third phase (phase III) of a clinical trial.

Objective: The objectives of this article are to discuss the recent progress in the development of new vaccines against TB; to provide an insight on the mechanism of vaccine-mediated specific immune response stimulation, and to debate on the interaction between vaccines and global interventions to end TB.

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<![CDATA[Prevalence of Latent Tuberculosis (LTB) Among Pregnant Women in a High Burden Setting in Sudan using Interferon Gamma (IFN- γ) Releasing Assay (IGRA)]]>https://www.eurekaselect.comarticle/92866Background: Accurate timing for diagnosis and treatment of latent tuberculosis (LTB) is important to reduce morbidity and mortality for both mother and child.

Objectives: To investigate the prevalence rate of LTB and its associated factors during pregnancy using gamma interferon (IFN- γ) release assay (IGRA).

Methods: A cross-sectional facility-based study carried out in Kassala hospital, Eastern Sudan between January and March 2015.

Results: Two hundred and forty-nine women were enrolled in this study and 18.1% (45/249) had confirmed positive for M. tuberculosis infection using IGRA. The mean age, parity and gestational age of the LTB patients were 29.6 (4.4), 2.2 (1.2) and 21.9 (8.8), respectively. The vast majority of these patients was of rural residence (72.7%), housewives (91.1%) and illiterate (73.3%). More than half (25, 55.6%) gave a history of contact with tuberculosis patients, 26.7% (12/45) were vaccinated and 11.1% (5/45) had a medical history of diabetes mellitus. In logistic regression model, while age, parity, education, occupation, size of family members, smoking, BCG status and medical history of diabetes mellitus were not associated with latent tuberculosis during pregnancy, history of contact with TB patients (OR=13.5; CI=5.6 to 32.5; P<0.001) and rural residence (OR=0.3; CI=0.1 to 0.7; P=0.006) was significantly correlated to LTB in pregnancy.

Conclusion: Thus, screening of all pregnant women living in high burden setting of tuberculosis is recommended even in the absence of overt clinical signs of the disease.

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<![CDATA[Nanotechnology-Based Approaches for Combating Tuberculosis: A Review]]>https://www.eurekaselect.comarticle/93620 <![CDATA[2D QSAR Analysis of Substituted Quinoxalines for their Antitubercular and Antileptospiral Activities]]>https://www.eurekaselect.comarticle/93626

Methods: The models developed showed good linear relationship (r2 = 0.71-0.88), with an internal predictive ability (q2> 0.61) and good external predictive ability (pred_r2>0.71). The compounds were separated into a training set on which regression was performed and a test set on which the predictive ability of the model was tested. Other statistical parameters including Ro2, Ro’2, k, k’ and Z- score were in the acceptable range.

Results and Conclusion: The descriptors obtained explained the necessity of spatial orientation of atoms including branching and adjacency, presence of electronegative groups, balance between lipophilic elements and their binding strengths.]]> <![CDATA[Benzothiazol Clubbed Imidazol-4-ones as Anti-fungal, Anti-tubercular and Anti-HIV-1 Agents: Their Synthesis and Molecular Docking Study]]>https://www.eurekaselect.comarticle/91667

Objective: The major aim of this study is to develop the new class of bezylidine candidate clubbed with benzothiazole with less toxicity and improved potency as antimicrobial, antitubercular and anti HIV-1.

Methods: The titled compounds were characterized by spectral studies (IR, 1H NMR, 13C NMR and Mass). In vitro antimycobacterium activity was carried out using Lowenstein-Jensen medium method and antimicrobial activity using the broth microdilution method. The anti HIV-1 reverse transcriptase activity was determined by the colorimetric MTT method and inhibition of virusinduced cytopathogenicity in MT-4 cells.

Results: Compound 4i (50 µM) showed better antifungal activity against A. clavatus. Compound 4g (50 µM) with 95% inhibition demonstrated good activity against M. tuberculosis H37Rv. Compound 4k showed CC50 (50 µM) against MT-4 (CD4+ Human T-cells containing an integrated HTLV-1 genome) cells by 50%, while 16 µM concentration value EC50 from the HIV-1 induced cytopathogenicity. Molecular docking study suggested that 4k interacted with the target with binding energy by Vina score (-10.3 Kcal/mol).

Conclusion: The preliminary in vitro evaluation results revealed that some of the compounds have promising antimicrobial activities as well as antitubercular potency. Among the various substituents on benzylidene, the nitro group was the most beneficial for improving the anti-HIV-1 activity. Docking result suggested that 4k compound could be acting as a non-competitive or weak inhibitor of Reverse Transcriptase (RT).]]> <![CDATA[Molecular Docking Study for Analyzing the Inhibitory Effect of Anti-inflammatory Plant Compound Against Tumour Necrosis Factor (TNF-α)]]>https://www.eurekaselect.comarticle/90188

Methods: In the present article, characterization of quercetin has been carried out to check its drug likeliness and molecular docking study has been carried out between TNF- α and quercetin by using AutoDock 4.2.1 software. Further, inhibitory effect of B. sapida fruit extract on RA plasma has been analysed through immunological assay ELISA.

Results: Our in-silico analysis indicated that quercetin showed non carcinogenic reaction in animal model and it may also cross the membrane barrier easily. We have studied the ten different binding poses and best binding pose of TNF-α and quercetin showed -6.3 kcal/mol minimum binding energy and 23.94 µM inhibitory constant. In addition to this, ELISA indicated 2.2 down regulated expression of TNF-α in RA compared to control.

Conclusion: This study may further be utilized for the drug designing studies to reduce TNF-α mediated inflammation in near future. This attempt may also enhance the utilization of this plant worldwide.]]> <![CDATA[Current Understanding of Interactions between Nanoparticles and ABC Transporters in Cancer Cells]]>https://www.eurekaselect.comarticle/89111

Methods: We undertook extensive search of PubMed databases for peer-reviewed literatures using focused review questions. The retrieved papers were mostly published within the 5 years (84 of 104) and all with an impact factor above 2. First, this review focused on the current knowledge of ABC transporters involved in MDR and their inhibitors. Then, we reviewed the most recent literature about the inhibitory effects of organic NPs’ excipients on ABC transporters and the direct interactions of inorganic NPs with ABC transporters. The major elements of obtained papers were described and classified depending on the structure of NPs.

Results: Both organic and inorganic NPs can inhibit the function of ABC transporters, but based on different mechanisms. The effects of organic NPs are caused by several excipients like surfactants, polymers, lipids and cyclodextrin. Meanwhile, inorganic NPs usually act as the substrates of ABC transporters and competitively inhibit the efflux of drugs. These phenomena are interesting and worth investigating.

Conclusion: The finding of this review confirmed the potential interactions between NPs and ABC transporters. These phenomena are interesting and worth investigating, and a knowledge of related mechanism would not only be important for the clinical therapies toward overcoming cancer MDR, but also help the treatment of other diseases like tuberculosis, AIDS, and central nervous system disorders, whose drugresistance was also related to ABC transporter-mediated efflux.]]> <![CDATA[New insights on Ethambutol Targets in Mycobacterium tuberculosis]]>https://www.eurekaselect.comarticle/88174

Objective: Based on the need to better investigate the complex mechanism of action of ethambutol, our study presented the proteome profile of M. tuberculosis after different times of ethambutol exposure, aiming to comprehend the dynamics of bacilli response to its effects. M. tuberculosis was exposed to ½ MIC of ethambutol at 24 and 48 hours. The proteins were identified by MALDI-TOF/TOF.

Results: The main protein changes occurred in metabolic proteins as dihydrolipoyl dehydrogenase (Rv0462), glutamine synthetase1 (Rv2220), electron transfer flavoprotein subunit beta (Rv3029c) and adenosylhomocysteinase (Rv3248c).

Conclusion: Considering the functions of these proteins, our results support that the intermediary metabolism and respiration were affected by ethambutol and this disturbance provided proteins that could be explored as additional targets for this drug.]]> <![CDATA[Recent Developments in Azole Compounds as Antitubercular Agent]]>https://www.eurekaselect.comarticle/91231 <![CDATA[Computational Studies of Molecular Targets Regarding the Adverse Effects of Isoniazid Drug for Tuberculosis]]>https://www.eurekaselect.comarticle/94376

Objective: Identification of the molecular targets responsible for differences in susceptibility to the adverse effects of isoniazid drug.

Method: Inverse docking was used to identify potential molecular targets of isoniazid in the human proteome. The molecular targets and the annotations obtained from inverse docking were compared with those obtained from PharmGKB variant annotations.

Results and Conclusion: The results of this study are consistent with and rationalize earlier biochemical, molecular and clinical studies that relate prevalence of isoniazid induced adverse effects to genetic polymorphisms in NAT2, GSTT1, GSTM1 and CYP*. The computational results of this study indicate that MAO, COMT and NNMT are additional potential targets related to variation in isoniazid induced adverse effects.]]> <![CDATA[In Vitro Anti-mycobacterial Activity of Three Medicinal Plants of Lamiaceae Family]]>https://www.eurekaselect.comarticle/91281

Methods: The essential oils were prepared by the standard method. The confirmed strains were obtained from the microbial collection of Tehran University of Medical Sciences. Minimum Inhibitory Concentrations (MICs) of essential oils of plants against mycobacterial strains were determined using standard broth microdilution method.

Results: MDR M. tuberculosis was completely inhibited by Z. multiflora at 78µg/ml concentration. S. rechingeri and S. khuzestanica also showed same anti-mycobacterial activity against MDR M. tuberculosis with MICs of 156 µg/ml. The MICs of the essential oils against M. tuberculosis H37Rv, M. kansasii and M. fortuitum were in the range from 39 to 156 µg/ml.

Conclusion: The studied medicinal plants showed notable effects against mycobacterial strains. Our results indicated that utilization of Lamiaceae family can be helpful for treatment of mycobacterial infections.]]> <![CDATA[Anti-Infective Peptides to Enhance the Host Innate Response: Design, Development and Delivery]]>https://www.eurekaselect.comarticle/94190

Conclusion: Inhibitors of the SPSB-iNOS interaction have therapeutic potential as a novel class of anti-infective agents. Various strategies are being pursued to target these peptide inhibitors to macrophages and deliver them to the cytoplasm of these cells. It will then be possible to assess the efficacy of such inhibitors in boosting the capacity of macrophages to destroy infectious pathogens.]]> <![CDATA[Kinase Targets for Mycolic Acid Biosynthesis in Mycobacterium tuberculosis]]>https://www.eurekaselect.comarticle/93990

Objective: Recent updates to the kinases and phosphatases involved in the regulation of MAs biosynthesis will be presented in this mini-review, including their known small molecule inhibitors.

Conclusion: Mycobacterial kinases and phosphatases involved in the MAs regulation may serve as a useful avenue for antitubercular therapy.]]> <![CDATA[Old Drugs and New Targets as an Outlook for the Treatment of Tuberculosis]]>https://www.eurekaselect.comarticle/85912

Objective: To extract the latest information on new mechanisms of action described or proposed for clinically used antitubercular drugs. To identify drugs from various pharmacodynamic groups as candidates for repurposing to become effective in combatting tuberculosis. Attention will be paid to elucidate the connection between repurposed drugs and new antituberculars in clinical practice or in clinical trials.

Methods: Scientific databases were searched for the keywords.

Results: We reviewed the latest aspects of usage and new mechanisms of action for both first-line and second-line antitubercular drugs in clinical practice. Further, we found that surprisingly large number of clinically used drugs from various pharmacodynamic groups have potential to be used in the treatment of tuberculosis, including antimicrobial drugs not typically used against tuberculosis, statins, CNS drugs (tricyclic phenothiazines, antidepressants, anticonvulsants), non-steroidal anti-inflammatory drugs, kinase inhibitors, and others (metformin, disulfiram, verapamil, lansoprazole). Repurposed drugs may become effective antituberculars, acting either by direct effects on mycobacteria or as adjunct, host-directed therapy.

Conclusion: In this review, we showed that proper research of old drugs is a very efficient tool to develop new antituberculars.]]> <![CDATA[Benzothiazole-based Compounds in Antibacterial Drug Discovery]]>https://www.eurekaselect.comarticle/86257 <![CDATA[Tuberculosis and HIV Coinfection–the Challenge in the Prevention, Detection and Treatment of Tuberculosis]]>https://www.eurekaselect.comarticle/91201

Objective: In this review we focused on the challenges of epidemiological and clinical feature of tuberculosis presented by the HIV coinfection.

Method: The article consists of a summary of the most important effects presented by the HIV coinfection on epidemiological and clinical feature of tuberculosis. The article analyzes and summary the causes for these challenges.

Results: The major challenges to strategy of TB control and clinical feature of TB-HIV coinfection are presented in this paper.

Conclusion: HIV/TB co-infection is synergic, interactive and reciprocal with significant impact. The infection of HIV and Mtb affect each other and the breakdown the immune function in TB/HIV coinfected individual. HIV infection has changed the strategy of TB control, however HIV increases global burden of TB, the reduction in the TB incidence rate is far from sufficient. Atypically clinical manifestations in TB/HIV co-infected patients and increased MDR-TB and XDR-TB contribute to the challenges in the diagnosis and treatment. Increased complexity of managing patients requires expertise in the clinical m knowledge. The focused efforts to control HIV-related TB are of great urgency. These findings will provide insight into the prevention, detection and treatment of tuberculosis and will guide advances towards tuberculosis control.]]> <![CDATA[Recent Highlights on the Synthesis of Pyrazoles with Antimicrobial Activity]]>https://www.eurekaselect.comarticle/92019

Methods: This review encompasses reports on the synthesis and antimicrobial evaluation of synthetic pyrazoles from the year 2012 to 2017, which were extracted from bibliographic databases such as PubMed, scielo, sciencedirect, scifinder, and scopus. The main keywords in our search were “pyrazole” and “antimicrobial activity”, in which we made efforts to include synthetic and biological methodologies that can be useful for laboratories of different levels of infrastructure. Moreover, inclusion/ exclusion criteria was applied to select quality reports which could demonstrate different tools of antimicrobial evaluation, focusing on the advances made in the area, such as evaluation in silico and exploration of the possible mechanism of action for active compounds.

Results: Thirty-four papers were included in this work, which was displayed chronologically from the year 2012 to 2017 in order to enhance the advances made in the area, with at least five reports from each year. We found that the most commonly tested bacterial strains are Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and from the year 2016 onwards Mycobacterium tuberculosis. The most common tested fungal strains are Candida albicans, Aspergillus flavus, and Aspergillus niger. The majority of articles expressed the antimicrobial results as a zone of inhibition, leading to the determination of the Minimum Inhibitory Concentration (MIC) and a probable mechanism of action for the most prominent compounds, considering cytotoxicity. Aromatic aldehydes and ketones are key reactants to obtain important precursors for the synthesis of pyrazoles, such as chalcones, together with alkyl or phenylhydrazines and thiosemicarbazide. A great variation in the reported MICs was found as there is no standard maximum limit, but many compounds exhibited antimicrobial activity comparable or better than standard drugs, from which 10 reports active compounds with MIC lower than 5 μg mL-1.

Conclusion: The findings of this work support the importance of pyrazole moiety in the structure of antimicrobial compounds and the versatility of synthetic methodologies to obtain the target products. Results clearly indicate that they are attractive target compounds for new antimicrobial drugs development. We hope that this information will guide further studies on continuing the search for more effective, highly active antimicrobial agents.]]>
<![CDATA[Application of Computational Techniques to Unravel Structure-Function Relationship and their Role in Therapeutic Development]]>https://www.eurekaselect.comarticle/94689 <![CDATA[Novel Diazenyl Containing Phenyl Styryl Ketone Derivatives As Antimicrobial Agents]]>https://www.eurekaselect.comarticle/93285

Objective: In this project, an attempt has been made to synthesize some derivatives of diazenyl containing phenyl styryl ketones and also their in vitro screening was conducted against Mycobacterium tuberculosis, Escherichia coli, Klebsiella pneumonia, Bacillus subtilis, Staphylococcus aureus, Aspergillus niger and Candida albicans.

Methods: Ten molecules were synthesized which are diazenyl containing chalcones. 4- aminoacetophenone was diazotised and piperidine was coupled with the formed diazonium chloride. Further, the acetoxy group underwent Claisen-Schmidt condensation with differently substituted aldehydes to form the final compounds- the chalcones. The proposed chemical structures were confirmed by different spectroscopic techniques like FTIR, 1H NMR and Mass spectroscopy. TLC was used to know that the reactants were exhausted and the formation of the product occurred. Sharp melting point of the compounds concludes the purity.

Results: The MIC of the compounds 3CP, 3DP, 3EP and 3GP is 20 times the MIC of the standard fluconazole drug against Aspergillus niger. The compound 3GP is as equipotent as the standard drug Pyrazinamide with MIC of 3.12 µg/ml against Mycobacterium tuberculosis.

Conclusion: The results are quite promising which on further studies may lead to drug molecules against different microorganisms. Especially, 3EP can be considered as a broad spectrum agent due to its potent activity against different microorganisms like Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Candida albicans.]]> <![CDATA[Design, Synthesis and Biological Profiling of Novel Phenothiazine Derivatives as Potent Antitubercular Agents]]>https://www.eurekaselect.comarticle/92035

Objective: The study aimed to carry out development of phenothiazine based antitubercular agents by modifying/removing the chemical group(s)/ linker(s) of chlorpromazine essential for exerting an antipsychotic effect.

Methods: The designed molecules were filtered with a cut-off of docking score < 2.0 Kcal/mol against dopamine receptors, so that their binding with the receptor would be reduced to produce no/ less antipsychotic effect. The molecules were then synthesized and screened against M. tuberculosis H37Rv. They were further screened against a gram-positive (S. aureus) and a gram-negative (E. coli) bacterial strains to evaluate the spectrum of activity. The ability of the compounds to cross the blood-brain barrier (BBB) was also analyzed. The compounds were further examined for cytotoxicity (CC50) against mammalian VERO cells.

Results: Compounds 14p, 15p and 16p were found to be the most effective against all the strains viz. M. tuberculosis H37Rv, S. aureus and E. coli with MIC of 1.56µg/ml, 0.98µg/ml and 3.91µg/ml, respectively. Further, BBB permeability was found to be diminished in comparison to chlorpromazine, which would ultimately reduce the unwanted antipsychotic activity. They were also found to be free from toxicity against VERO cells.

Conclusion: The designed strategy, to enhance the antitubercular activity with concomitant reduction of dopamine receptor binding and BBB permeability was proved to be fruitful.]]> <![CDATA[Synthesis, Screening and Docking Analysis of Novel Benzimidazolium and Benzotriazolium Compounds as Potent Anti Tubercular Agents]]>https://www.eurekaselect.comarticle/92307

Objective: One of the biggest problems of Tuberculosis is the lack of effective treatments. Bedaquiline (2013) and Delaminid (2014) are the only two agents approved for TB after Rifampicin. This clearly shows the need for new lead molecules to fight against TB.

Methodology: A series of benzimidazolium and benzotriazolium derivatives were synthesized and the structures were confirmed by their IR, 1H NMR,13C NMR and mass spectral data. They were tested for in vitro antitubercular activity by MABA Assay, MTT Assay and axenic culture assay. To determine selective TB activity, they were also tested for antimicrobial activity and cytotoxicity. Docking simulations and drug-inhibitor combination studies were conducted to know the probable mechanism of action.

Results: Among the synthesized compounds B10, B11, B13, B14, B22, B23, B24, B25, B26 and B27 showed excellent anti TB activity with an MIC 3.12-0.8 µg/mL. Among these, compound 1,3- bis(4-chlorobenzyl)-1H-benzo[d]imidazol-3-ium chloride (B11) has shown selective anti TB activity against Mycobacterium tuberculosis H37Rv (0.8µg/mL) in MABA assay. This compound hasn’t shown any antimicrobial (at 100μg/mL) and cytotoxicity (at 10µM). Docking studies and drug-inhibitor combination studies indicated that the compounds might act via enzymes involved in the cell division process.

Conclusion: In conclusion, we synthesized molecules with potent and selective anti TB activity.]]> <![CDATA[Interfacial Phenomenon Based Biocompatible Alginate-Chitosan Nanoparticles Containing Isoniazid and Pyrazinamide]]>https://www.eurekaselect.comarticle/91246

Objective: The aim of this study is to fabricate alginate-chitosan nanoparticles (AL-CS NPs) under appropriate conditions using ionic gelation method. The use of natural polymers in nanoparticle fabrication has a vast application due to their biodegradability, biocompatibility and nontoxic nature. Ionic gelation method involves the interaction between macromolecules with opposite charged ionizable groups forming polyelectrolyte complex. Hence, it is rational to formulate natural polymerbased sustained release nano-particulate matrix to improve patient adherence, reducing dose frequency and drug toxicity.

Method: The formulations were based on 32 factorial designs. Nanoparticles of combined drug (Isoniazid- INH and Pyrazinamide-PYZ) were fabricated using natural polymer. Formulation process involved the use of pregelated sodium alginate followed by ionic gelation with chitosan. Pregelation of sodium alginate included calcium chloride. The effects of sodium alginate concentration and chitosan concentration on particle size, zeta potential, entrapment efficiency and in vitro drug release were studied.

Results: Optimized Batch-3s showed particle size 539.7 ± 2.33 nm, zeta potential -26.4 ± 0.55 mV, and entrapment efficiency is 70.21 ± 0.24% and 73.45 ± 0.21% of INH and PYZ, respectively. Dissolution release study of Batch-3s in 7.4 pH phosphate buffer exhibited the initial burst of 5.04 ±0.45% and 19.68 ± 0.87% at 0.25 hrs followed by slow, sustained release of drug 74.53 ± 2.53 and 57.87 ± 2.04% at 10 hrs of INH and PYZ, respectively.

Conclusion: It concluded that chitosan (CS) and sodium alginate (AL) concentration are rate-limiting factors in formulation development. Natural polymer based combined drug nano-particulate system could be an innovative and optimistic approach in the treatment of TB.]]> <![CDATA[Combinatorial Design of Molecule using Activity-Linked Substructural Topological Information as Applied to Antitubercular Compounds]]>https://www.eurekaselect.comarticle/90306

Objective: To develop a method using graph-theoretical techniques for generating structures of antitubercular compounds combinatorially from activity-linked substructural topological information, predict activity and prioritize and screen potential drug candidates.

Methods: Activity related vertices are identified from datasets composed of both active and inactive or, differently active compounds and structures are generated combinatorially using the topological distance distribution associated with those vertices. Biological activities are predicted using topological distance based vertex indices and a rule based method. Generated structures are prioritized using a newly defined Molecular Priority Score (MPS).

Results: Studies considering a series of Acid Alkyl Ester (AAE) compounds and three known antitubercular drugs show that active compounds can be generated from substructural information of other active compounds for all these classes of compounds. Activity predictions show high level of success rate and a number of highly active AAE compounds produced high MPS score indicating that MPS score may help prioritize and screen potential drug molecules. A possible relation of this work with scaffold hopping and inverse Quantitative Structure-Activity Relationship (iQSAR) problem has also been discussed.

Conclusion: The proposed method seems to hold promise for discovering novel therapeutic candidates for combating Tuberculosis and may be useful for discovering novel drug molecules for the treatment of other diseases as well.]]> <![CDATA[Recurrent Episodes of Pericardial Effusion as Isolated Manifestation of Tuberculosis: Case Report]]>https://www.eurekaselect.comarticle/84216

Methods: This is a case report of a previously healthy 32-years old male with tuberculous induced pericardial effusion as isolated manifestation. The only known exposure of tuberculosis was a brother with whom the patient did not have physical contact during the last year. The pericardial effusion repeatedly appeared after being drained a total of three times. Due to recurrent episodes of pericardial effusion, severe thickening of the pericardium, pericardial adherences and increasing affection on the heart, pericardiectomy was ultimately performed.

Results: Biochemical examination, chest X-ray, computed tomography of thorax and abdomen and cytology report did not reveal any signs of malignancy, connective tissue disease or other infections including extra-pulmonary/pulmonary tuberculosis. However, the pericardial biopsy was Polymerase Chain Reaction positive (PCR) for tuberculosis DNA and showed granulomatous inflammation with necrosis. After 6 months anti-tuberculous therapy, biochemical parameters, LVEF and the clinical condition of the patient were normalized.

Conclusion: Tuberculosis can be difficult to diagnose when it only manifests as pericardial effusion especially if the time for exposure is long before the appearance of symptoms and admission.]]> <![CDATA[Pulmonary Sarcoidosis Presenting with Miliary Opacities]]>https://www.eurekaselect.comarticle/92196

Discussion: Miliary Tuberculosis (TB) was initially suspected, despite the direct microscopic examination from bronchoalveolar lavage was negative for acid-fast bacilli because imaging showed miliary opacities, and transbronchial lung biopsy revealed the presence of typical caseating granulomas. Antitubercular treatment with the classic four-drug regimen was initiated. However, the patient did not improve and cultures were negative for Mycobacterium growth. The diagnosis of sarcoidosis was made only after a negative culture and clinical and histopathological re-evaluation of the case.

Conclusion: Although miliary sarcoidosis is rare, physicians should consider sarcoidosis in the differential diagnosis with conditions like tuberculosis, malignancy, and pneumoconiosis when patients present with miliary opacities who do not respond to the traditional treatment.]]> <![CDATA[Recent Advancement in the Diagnosis and Treatment of Leprosy]]>https://www.eurekaselect.comarticle/93965

Methods: A negligible amount of advancements has been made in last few decades which includes the tools of diagnosis, causes, treatment, and genetic studies of the bacterium (Mycobacterium leprae) that causes leprosy. The diagnosis of leprosy at earlier stages is important for its effective treatment. Recent studies on vitamin D and its receptors make leprosy diagnosis easier at earlier stages. Skin biopsies and qPCR are the other tools to identify the disease at its initial stages.

Results: Until now a specific drug for the treatment of leprosy is not available, therefore, Multi-Drug Therapy (MDT) is used, which is hazardous to health. Besides Mycobacterium leprae, recently a new bacterium Mycobacterium lepromatosis was also identified as a cause of leprosy. During the last few years the genetic studies of Mycobacterium leprae, the role of vitamin D and vitamin D receptors (VDR), and the skin biopsies made the treatment and diagnosis of leprosy easier at early stages. The studies of micro RNAs (miRNAs) made it easy to differentiate leprosy from other diseases especially from tuberculosis.

Conclusion: Leprosy can be distinguished from sarcoidosis by quantitative study of reticulin fibers present in skin. The treatment used until now for leprosy is multi-drug treatment. The complete genome identification of Mycobacterium leprae makes the research easy to develop target specified drugs for leprosy. Rifampicin, identified as a potent drug, along with other drugs in uniform multi-drug treatment, has a significant effect when given to leprosy patients at initial stages. These are effective treatments but a specific drug for leprosy is still needed to be identified. The current review highlights the use of modern methods for the identification of leprosy at its earlier stages and the effective use of drugs alone as well as in combination.]]> <![CDATA[Fabrication and Characterization of Chitosan Nanoparticles: A controlled Release Approach Towards Tuberculosis Chemotherapy]]>https://www.eurekaselect.comarticle/92169

Objective: To formulate combined drug chitosan nanoparticles of antitubercular drugs (Isoniazid-INH and Pyrazinamide-PYZ) to get additive effect on Mycobacterium tuberculosis. Nanoparticles are colloidal system that enhances effective permeation through cell membrane, stability in blood stream and controlled release of drug. Hence, it is emerging as a new weapon in drug delivery field.

Methods: The 32 factorial design was used to formulate nanoparticles by ionic gelation method using Chitosan (CS) and sodium tripolyphosphate (TPP) with ratio 3:1 (CS:TPP::v/v) in pH range 4.6 to 4.8. The effect of CS and TPP concentration on particle size, zeta potential, entrapment efficiency and in vitro drug release were studied.

Results: Optimized batch 8N showed particle size 414.3 ± 2.71 nm, zeta potential 26.52 ± 0.67mV, PDI (poly dispersity index) 0.296 and entrapment efficiency of INH and PYZ 55.29 ± 0.06% and 63.14 ± 0.29% respectively. Dissolution release study of 8N formulation at pH 7.4 showed initial burst release of 20.28 ± 1.43% and 23.62 ± 1.07 at 0.25 hrs followed by controlled release up to 84.82 ± 2.54% and 61.48 ± 1.52% by INH and PYZ for 14 hrs.

Conclusion: The study concluded that CS and TPP concentration were rate limiting factors in optimizing formulation development. Combined drug nanoparticle system has an innovative and optimistic approach towards the enhancement of therapeutic efficacy and reduction undesirable effects of antitubercular drug.]]> <![CDATA[Virtual Screening and in vitro Antibacterial Activity for the Identification of Novel Inhibitors of Mycobacterium tuberculosis Methionine Aminopeptidase]]>https://www.eurekaselect.comarticle/91273

Objective: To screen the potential MetAP of Mycobacterium tuberculosis inhibitor by in silico virtual screening of ZINC database and evaluate the best potential lead molecule by in vitro studies.

Results and Conclusion: In this research, we used the FlexX program to screen collections of chemical compounds against the protein target. Before performing the molecular docking, FlexX was validated by tow tests to determine the reproducibility of docking program. After the virtual screening, nine chemical compounds of the top hits predicted were purchased and evaluated in vitro for their antibacterial activities against Mycobacterium smegmatis, using the paper disc diffusion method. Among the studied compounds, only the compound ZINC04785369 inhibited the bacterial growth and could be promising antimycobacterial agents. All these may provide something useful for the development of the potent inhibitors.]]> <![CDATA[Bedaquiline: A New Hope for Shorter and Better Anti-Tuberculosis Regimens]]>https://www.eurekaselect.comarticle/84220

Methods: Currently available anti-MDR and XDR regimens are long-lasting and expensive, need high adherence and are undermined by a high frequency of adverse drug events, thus leading to a low success rate; furthermore, in the last 50 years only two new molecules, bedaquiline (BDQ) and delamanid, have been approved and released for the treatment of MDR-TB.

Results: BDQ, patent number US 7,498,343B2, is a diarylquinoline anti-mycobacterial drug, active regardless of the state of MTB; in fact, its efficacy is conserved against replicating and non-replicating bacilli, despite extracellular or intracellular location. BDQ has been approved by the Food and Drug Administration (FDA) only for combination treatment of pulmonary multidrug-resistant tuberculosis (MDR-TB), in adult patients, when an effective treatment cannot be provided otherwise due to resistance or poor tolerability; however, due to high bactericidal activity, BDQ may be used in future to treat extrapulmonary tuberculosis and Mycobacterium other than tuberculosis (MOTT) infection.

Conclusion: BDQ may play a major role to get closer to TB eradication and to ensure higher retention in care, even in fully susceptible MTB strains and against non-replicating mycobacteria in latent-TB, providing an alternative to standard regimen.]]> <![CDATA[Lung Cancer- Current Clinical Profile and Diagnostic Challenges]]>https://www.eurekaselect.comarticle/91331

Aims and Objectives: The aim of this study was to analyze the current clinico-pathological profile and epidemiological trends in lung cancer patients from a single tertiary care centre with emphasis on given on gender association and delay in detection due to misdiagnosis as tuberculosis.

Materials and Methods: A retrospective analysis of the data of in-patients diagnosed as Primary lung cancer in the department of pulmonary medicine at SDSTRC& Rajiv Gandhi institute of chest diseases, Bengaluru, Karnataka from August 2015 to September 2017.

Results: Lung cancer study is still a disease predominant in old age males. Smoking is one of the major causative factors. In Non smokers, females and young age group (<40yrs) adenocarcinoma was commoner than squammous cell carcinoma.17 patients (16.5%) were mis-diagnosed as tuberculosis before the definitive diagnosis was made.

Conclusion: Due to widespread prevalence of tuberculosis, lung cancer poses a diagnostic challenge. A significant number of lung cancer patients in our country still continue to be misdiagnosed as tuberculosis. Poor diagnostic resources and economic constraints along with low clinical suspicion lead to delay in diagnosis of lung cancer resulting in poor prognosis and survival.]]> <![CDATA[Sarcoidosis or Tuberculosis? Detecting Mycobacterium tuberculosis Complex DNA in Sarcoidosis Granulomas]]>https://www.eurekaselect.comarticle/91333

Methods: Formalin-Fixed Paraffin-Embedded (FFPE) tissues of 33 patients with sarcoidosis were analyzed for the presence of mycobacterial DNA. Genomic DNA extraction was done by QIAamp DNA FFPE Tissue Kit. Polymerase chain reaction using insertion element IS6110 of M. tuberculosis complex (MTC) was applied by commercial kits (GeneProof) for all individuals. The results were compared with 27 patients with tuberculosis and 5 other patients associated with granulomatous disease of the lung. All cases had confirmed granulomatous inflammation in their histopathological examination.

Results: In this study, the IS6110 repetitive DNA element of (MTC) was not detected in any of the tissue samples from the patients with sarcoidosis. Of the 33 sarcoidosis patients, 30 (90.1%) had negative results for IS6110 and despite the repeated attempts of DNA extraction for three patients (9.1%), strong inhibitor made constant negative outcomes. In contrast, in patients with tuberculosis, 22 (81.5%) had positive results, three had (11.1%) negative results and 2 patients (7.4%) showed negative results with strong inhibitor. IS6110 was not found in any of the control group patients.

Discussion: This study does not support the presence of M. tuberculosis in tissues of patients with sarcoidosis as a microbial pathogen or trigger of the immune response. Due to difficulties in diagnosis of sarcoidosis and different methods for diagnosis of M. tuberculosis, the impact of M. tuberculosis as a possible aetiological agent in sarcoidosis has been the point of debate.]]> <![CDATA[Synthetic Versus Enzymatic Pictet-Spengler Reaction: An Overview]]>https://www.eurekaselect.comarticle/91095

Objective: The present review is a strenuous effort to assemble information mainly focusing on synthetic as well as biological Pictet-Spengler reactions catalysed by enzymes called Pictet-Spenglerase.

Conclusion: In the present review, the recent advances in the PS-mediated synthesis of diverse heterocycles such as tetrahydroisoquinoline, tetrahydro-β-carbolines, tetrahydroimidazopyridines and other fused heterocycles via chemical as well as enzymatic pathways have been covered. The compounds find their scope as medicinal agents for the treatment of cancer, tuberculosis, bacterial infection, leishmanial, etc. The compilation is expected to provide a mechanistic insight to chemists to enhance the reaction condition, yields and another parameter to ensure the safe and inexpensive reaction conditions considering the “Green-Concept” of chemistry.]]> <![CDATA[Medicinal Botanicals in the Traditional Medicine of the Veps Used for Bronchial Infections]]>https://www.eurekaselect.comarticle/89972 <![CDATA[Advances in Computational Studies of Potential Drug Targets in Mycobacterium tuberculosis]]>https://www.eurekaselect.comarticle/92206 <![CDATA[Synthesis, In silico Molecular Docking and Pharmacokinetic Studies, In vitro Antimycobacterial and Antimicrobial Studies of New Imidozolones Clubbed with Thiazolidinedione]]>https://www.eurekaselect.comarticle/90464

Objective: In this report, we have designed and synthesized azole scaffolds with good antitubercular activities as there is a real need to develop new candidates with less toxicity and more efficiency toward pathogen. The obtained antimycobacterial activity data have been validated in the terms of ligand-protein interaction and were also analyzed for ADME properties to determine their potential to build up as good oral drug candidates.

Methods: All the synthesized compounds have been established by elemental analysis, IR, 1H NMR, 13C NMR and Mass spectral data. In vitro antimycobacterial activity was carried out against (M. tuberculosis) H37Rv strain using Lowenstein-Jensen medium and antimicrobial activity against two gram-positive bacteria (S. aureus, S. pyogenes), two gram-negative bacteria (E. coli, P. aeruginosa) and three fungal species (C. albicans, A. niger, A. clavatus) using the broth microdilution method. In silico molecular docking studies were carried out using Glide (grid-based ligand docking) program incorporated in the Schrödinger molecular modeling package by Maestro 11.0 and ADME properties of synthesized compounds was performed using DruLito software.

Results: Compounds 3a, 3b, 3d, 3g, 3i and 3n exhibited promising antimicrobial activity whereas compound 3n showed very good antimycobacterial activity along with Gilde docking score (-8.864) and with the one violation in Lipinski's rule of five.

Conclusion: The wet lab result for compound 3n along with Glide XP docking score and the calculated ADME parameters give the best choice for the preparation of new derivatives in order to improve antitubercular activity in future with more improved potency.]]> <![CDATA[Carbazole: A Potent Scaffold for Antitubercular Drugs]]>https://www.eurekaselect.comarticle/88679 <![CDATA[Synthetic Aspects and First-time Assessment of 2-amino-1,3-selenazoles Against Mycobacterium tuberculosis]]>https://www.eurekaselect.comarticle/88441

Methods: In this work, we investigated the formation of 2-aminoselenazoles on various organic solvents and in water, under catalyst-free conditions. Moreover, these molecules and their 2-aminothiazoles analogues were assessed in vitro for their antitubercular activity against Mycobacterium tuberculosis and the results compared.

Results: Instant reactions were observed when using polar aprotic solvents and all selenazoles were synthesized in water using sonochemistry. Furthermore, two selenazoles and one thiazole displayed activity in the µM range and the selenium heterocycles seems to be more potent than their sulphur analogues.

Conclusion: This is the first study of selenazoles against M. tuberculosis. It is noteworthy that 2-amino-1,3-selenazoles are interesting synthetic intermediates that could be incorporated into novel prototypes against tuberculosis.]]> <![CDATA[Cycloserine Induced Suicidal Tendencies and Kanamycin Induced Ototoxicity in Indian MDR-TB Patient: A Case Report]]>https://www.eurekaselect.comarticle/90931

Case Report: We present a case report on Cycloserine induced Suicidal tendencies and Kanamycin induced decrease in hearing sensation in Indian MDR-TB patient. A 55-year-old male patient who was diagnosed with MDR-TB was prescribed with category IV anti-tubercular therapy. Within one month of initiation of therapy, he developed repeated suicidal thoughts, joint pain, restlessness, depression, constipation, insomnia, tinnitus and a decrease in hearing sensation.

Results and Discussion: Cycloserine and kanamycin were closely associated with suicidal tendency and tinnitus followed by a decrease in hearing sensations respectively. On causality assessment using WHO-UMC Causality assessment scale, Adverse Drug Reaction with Cycloserine was found to be certain and for kanamycin, ADR was found to be possible.

Conclusion: Early management of such fatal ADR can improve the compliance, thus preventing the relapse of infection as well as improving therapeutic outcome in Tuberculosis patients.]]> <![CDATA[Phenothiazine: A Better Scaffold against Tuberculosis]]>https://www.eurekaselect.comarticle/81862 <![CDATA[Computational Determination of the Effects of Bacteriophage Bacteriophage Interactions in Human Body]]>https://www.eurekaselect.comarticle/86440

Method: This research paper presents a method to detecting the Bacteriophage-Bacteriophage Interaction. This method is implemented based on Domain-Domain Interactions model and it was used to infer Domain-Domain Interactions between the bacteriophages injected in the human body at the same time.

Results: By testing the method over bacteriophages that are used to treat tuberculosis, salmonella and virulent E.coli, many interactions have been inferred and detected between these bacteriophages. Several effects were detected for the resulted interactions such as: playing a role in DNA repair such as nonhomologous end joining, playing a role in DNA replication, playing a role in the interaction between the immune system and the tumor cells and playing a role in the stiff man syndrome. We revised all patents relating to bacteriophage bacteriophage interactions and phage therapy.

Conclusion: The proposed method is developed to help doctors to realize the effect of simultaneously injecting different bacteriophages into the human body to treat different diseases.]]> <![CDATA[Synthesis and Antibacterial/Antitubercular/Antioxidant Activities of Compounds Containing Fluoroquinolone Ring Linked to a 4-thiazolidinone Moiety]]>https://www.eurekaselect.comarticle/87632

Methods: A series of new compounds containing fluoroquinolone ring linked to a 4-thiazolidinone moiety were synthesized and evaluated for their potential pharmacological properties. The ZnCl2 mediated construction of 4-thiazolidinone ring via the condensation/cyclization of Schiff bases with thioglycolic acid was used as a key step for the multi-step synthesis of this class of compounds.

Results: When tested for antibacterial, antifungal, antitubercular activities in vitro and antioxidant activities several of these compounds showed good activities. Two compounds showed activities against both gram-(+) and gram-(-) strains and Mycobacterium smegmatis H37Rv ATCC 27294 (MTB) with MIC 16.28 and 27.86 µM, respectively. They also showed free radical scavenging properties with IC50 values in the range 23-33 μM and are appeared to be promising.

Conclusion: Our study revealed that the molecular framework presented here could be a useful template for the identification of novel small molecules as promising antimicrobial / amtitubercular agents.]]> <![CDATA[Synergistic Interplay of The Co-administration of Rifampin And Newly Developed Anti-TB Drug: Could It Be a Promising New Line of TB Therapy?]]>https://www.eurekaselect.comarticle/91709

Methods/Results: We provide an atomistic mechanism of Rifampin resistance in a single active site mutating Mycobacterium tuberculosis RNA polymerase, using a recently resolved crystal structure. We also unravel the structural interplay of this mutation upon co-binding of Rifampin with a novel inhibitor, D-AAP1. Mutation distorted the overall conformational landscape of Mycobacterium tuberculosis RNA polymerase, reduced binding affinity of Rifampin and shifted the overall residue interaction network of the enzyme upon binding of only Rifampin. Interestingly, co-binding with DAAP1, though impacted by the mutation, exhibited improved Rifampin binding interactions amidst a distorted residue interaction network.

Conclusion: Findings offer vital conformational dynamics and structural mechanisms of mutant enzyme-single ligand and mutant enzyme-dual ligand interactions which could potentially shift the current therapeutic protocol of Tuberculosis infections.]]> <![CDATA[Serum and Bronchoalveolar Lavage Fluid 25(OH)Vitamin D3 Levels in HIV-1 and Tuberculosis: A Cross-Sectional Study from a Tertiary Care Center in North India]]>https://www.eurekaselect.comarticle/90736

Objective: The primary objective was to assess the level of 25D3 in serum and BALF of subjects and look for a significant difference among patients and controls. The secondary objective was to find a correlation between serum and BALF 25D3 levels.

Methods: We performed a cross-sectional study with subjects divided into four groups: Controls (group 1), HIV positive without active TB (group 2), active TB without HIV (group 3), and HIV-TB coinfection (group 4). BALF and serum 25D3 levels were compared between the groups.

Results: Among the 149 (an immunomodulator) successive subjects enrolled, there were 40 subjects in group 1 (HIV-TB-), 48 in group 2 (HIV+TB-), 37 in group 3 (HIV-TB+), and 24 in group 4 (HIV+TB+). Females constituted 31.6% of the study subjects. In groups 3 and 4, there were significantly lower serum 25D3 levels compared to group 1 (p-value group 3: 0.002; group 4: 0.012). In groups 2, 3, and 4, there were significantly lower BALF 25D3 levels compared to group 1 (p-value group 2: 0.000; group 3: 0.000; group 4: 0.001). There was a significant correlation between serum and BALF 25D3 levels (Spearman’s rank correlation coefficient 0.318, p-value = 0.0001).

Conclusion: Lower levels of serum and BALF 25D3 were observed in HIV, TB, and HIV-TB coinfected patients. Localized deficiency of vitamin D metabolites might be associated with increased vulnerability to TB infection.]]> <![CDATA[DNA-Minor Groove Binding Agents as Anti-Tubercular Probes. Old Tools for a New Challenge?]]>https://www.eurekaselect.comarticle/91065

This review describes the structural features of the DNA-minor groove, the requirements for small molecules to bind to this site and the remarkable biophysical and antibacterial properties of DNA-minor groove binding agents, including netropsin, distamycin and their poly-heterocyclic analogues, diamidines, benzimidazole-containing molecules, duocarmycins and pyrrolo[2,1-c][1,4]benzodiazepines (PBDs). Furthermore, the ability of selected heterocyclic-polyamides and PBDs to significantly inhibit the growth of pathogenic, slow-growing M. tuberculosis and other non-pathogenic mycobacterial strains is highlighted. In summary, DNA-minor groove binding agents may serve as molecular scaffolds for the design of highly efficient probes to treat M. tuberculosis infections.]]> <![CDATA[Spoligotyping for Identification of Pulmonary Tuberculosis with Type 2 Diabetes Mellitus Profiles in Warangal, T.S.]]>https://www.eurekaselect.comarticle/90709

Methods: The study was carried out in diabetic type 2 patients suspected with pulmonary tuberculosis infections, Warangal, India. Spoligotyping was used for identification, detection and characterization of M. tuberculosis complex bacteria in clinical samples. This method is based on polymerase chain reaction (PCR) amplification of a highly polymorphic direct repeat locus in the M. tuberculosis genome. It is helpful in detecting causative bacteria and in providing epidemiologic information on genotyping strain identities.

Results: Based on the chest X-Ray of 200 diabetic patients suspected with pulmonary infections, we found 26 infiltrates, 30 cavitation, 28 miliary shadows, 35 pleural effusion, 46 mediastinal lymphadenopathy and 35 were confirmed for the extent of lesions, which supported us to further screen for pulmonary tuberculosis of 200 subjects tested, 113 were males, 85 were females and 2 were children. All 200 subjects were tested for pulmonary tuberculosis, 36 were positive by smear microscopy and 20 were culture positive. Phenotypic and genotypic variations were found for all the 20 identified clinical isolates, by conventional and molecular methods of 20 clinical isolates, 4 MDR-TB were identified based on the Drug Susceptibility Test for first-line drugs. Of 20 clinical isolates, we took 10 clinical isolates (4-were MDR-TB and 6- were MTB) and 1- was control sample of H37RV used for spoligotyping and showed different patterns Bejing (1) and Lineages of East Asian, of family EA13(2) and Lineages of Indo-Oceanic, of family LAM1(1) and Lineages of Euro-American and 6 were found to be MTB of family 33(2) and Lineages of Indo-Oceanic, of family CAS(4) and Lineages of Un-known family. CAS (Central Asian) of M.tuberculosis strains showed more prevailing spoligotype pattern in Diabetic Pulmonary Tuberculosis patients.

Conclusion: Implementing such a method in clinical settings would be useful in surveillance of tuberculosis transmission and in interventions to prevent further spread of this disease among the Diabetic Pulmonary Tuberculosis co-infections.]]> <![CDATA[Guanidinyl and Amide Conjugated Benzothiazoles as Potential Anti- Tubercular Agent and their Cytotoxicity Study]]>https://www.eurekaselect.comarticle/89969

Methods: The anti-mycobacterium study indicates that all the synthesized benzothiazole compounds were appreciably active and some of the compounds have MIC values lower than the standard drugs. Benzothiazoleguanidinyl derivatives (13a, 13b and 13f) showed the excellent activity with MIC values 1.6 µg/mL. The guanidinyl group and electron donating group present in the molecule interacts with the microorganism and arrest the further growth, indicating excellent activity by these compounds. These benzothiazole derivatives were also tested for cytotoxicity against MCF-7 and KB Mouth cell lines by MTT assay and they were found to be moderately active.

Results: For the KB-Mouth cell lines, diamide compounds (9a-9h) have remarkable activity and they showed IC50 values at 10 µg/mL. Compared to benzothiazole diamides, Benzothiazole guanidinyl compounds selectively acted as a good anti-mycobacterium agent.

Conclusion:In order to rationalize the in-vitro anti-tuberculosis activity, we carried out molecular docking studies with enoyl acyl carrier reductase (InhA) of M. tuberculosis and they exhibited remarkable docking scores from -5.85 to -9.27, which was comparable with the positive control Isoniazid (INH) with -6.61 as the docking score and showed less affinity towards the DprE1 protein.]]> <![CDATA[Fabrication and Characterization of Oral Dissolving Films for Tuberculosis Drug Delivery]]>https://www.eurekaselect.comarticle/82911

Materials and Methods: Three polymers such as poly(vinyl alcohol) (PVA), gelatin and chitosan were evaluated for their film forming property. Glycerin was used as plasticizer with different concentrations to find the effect of plasticizer on disintegration time of the polymer. The oral films were prepared by solvent casting method. FT-IR and UV-Vis analysis were employed to confirm the presence of drugs. Drug release studies were performed in simulated saliva solution.

Result: The performance of the films was evaluated with respect to thickness, weight uniformity, in vitro disintegration time, moisture uptake, moisture loss and folding endurance. Poly (vinyl alcohol) showed better film forming property than other polymers. The antimicrobial activity of the films was analyzed by well diffusion method.

Conclusion: The films prepared with 3% PVA with 5% plasticizer concentration showed minimum disintegration time (17 Seconds) which is highly suitable for oral drug delivery applications. This results in a new approach of TB drug delivery which reduces the complications in swallowing the tablets by elderly and pediatric people.]]> <![CDATA[Multi-Target Antitubercular Drugs]]>https://www.eurekaselect.comarticle/90740 <![CDATA[Identification of N-Benzylated Indole Mannich Bases as Potential Anti TB Agents by Using Computational Studies and Molecular Hybridization Technique]]>https://www.eurekaselect.comarticle/89899

Methods: In the present study, we used virtual screening method with a combination of molecular hybridization technique to design N-benzylated Indole Mannich bases as potent anti-TB agent based on BM212 pharmacophore. The library of designed molecules was prepared and screened using BM212 model. The top 5 ‘hit’ molecules were selected (with good TC score >1.15), synthesized and screened for anti TB activity by MABA assay method.

Results and Conclusion: All the compounds showed excellent anti TB activity, of which 4 compounds have shown MIC ≤12.5 µg/mL. Our protocol could help in the designing of newer anti-TB agents with better bioactivity profile.]]> <![CDATA[Synthesis, Biological Evaluation and Computational Study of New Quinoline Hybrids as Antitubercular Agent]]>https://www.eurekaselect.comarticle/86543

Methods: The designed molecules were synthesized by multi-step synthetic protocol and structures of compounds were confirmed by NMR, Mass and Elemental analysis. The synthesized derivatives were screened for antitubercular activity against Mycobacterium tuberculosis using Microplate Alamar Blue Assay (MABA). The antioxidant activity and cytotoxicity were also evaluated using 1,1-Dipheny-1-picrylhydrazyl (DPPH) radical scavenging and Sulforhodamine B (SRB) assay, respectively. The molecular docking studies were performed in Glide v5.6 (Schrodinger).

Results: Among the synthesized derivatives, the compounds 6d and 7d displayed promising antitubercular activity, with MIC value of 18.27 and 15.00 µM respectively and are relatively nontoxic to HeLa cell line. The synthesized compounds were found to have potential antioxidant activities with IC50 range of 73.47-123.46 µM. The molecular docking study, physicochemical and pharmacokinetic properties prediction study suggested that the synthesized derivatives have potential for development of good drug candidate.

Conclusion: Herein, we designed and synthesized a series of new quinoline pharmacophores appended with isoniazid and linezolid-like fragment as a promising strategy for the development of quinoline derivatives with potent biological activities.]]> <![CDATA[Synthesis, Characterizations and Microbial Studies of Novel Mannich Products Using Multicomponent Reactions]]>https://www.eurekaselect.comarticle/82992

Methods: The present methodology deals with Multicomponent reaction, in which, the mixture of 2,4- dihydroxybenzophenone 1.07 gm (0.005 M), 2-chloro-6-methoxyquinoline-3-carboxaldehyde 1.105 gm (0.005 M), with various amines 0.30 gm (0.005M) and EAN 30 ml (1 M) was stirred at 80°C temperature. The completion of reaction was monitored by TLC by using (chloroform/methanol, 70:30). On completion of the reaction, the reaction mixture was extracted thrice with 20 ml ethyl acetate. The extract was dried over anhydrous sodium sulfate, evaporated under vacuum and the residue was purified via recrystallisation from methanol or ethyl acetate to obtain pure new Mannich products 4(d1-d13). All synthesized compounds were screened for their in vitro antibacterial activity by using the agar dilution technique.

Results: The promising results obtained using 1M EAN as catalyst at the 80°C temperature encouraged us to investigate the feasibility of solvent-free MCRs protocol for the synthesis of new Mannich products 4(d1-d13). The recovery and recyclability of EAN were investigated for the synthesis of new Mannich products 4(d1-d13). It was found that, recycled ionic liquid was used up to four to five times without the loss of catalytic activity. The high yield (90-95%) of this products was observed at milder reaction condition compared to the other ionic liquid which rationalized due to high acidity associated with it (pH=5) along with its capacity to absorb water formed during the course of the reaction. All the compounds showed very good activity accept 4d13, especially against P. aeruginosa MTCC 1688 (MIC=25- 75 µg/mL), E. coli MTCC 443 (MIC = 25-100 µg/mL) and S. aureus MTCC 96 (MIC=25–75 µg/mL) whereas, 4d3 and 4d12, were found to be more potent rather than standard drugs Chloramphenicol and Ciprofloxacin. All the compounds showed excellent antifungal activity against C. albicans MTCC 227 (MIC=75-100 µg/mL) and A. niger MTCC 282 (MIC=75-100 µg/mL) whereas, 4d2 to 4d7 were found more potent rather Nystatin and Griseofulvin. Antituberculosis activity of all the compounds showed excellent activity 0.10 µg/mL rather than standard drug isoniazide (0.20 µg/mL) accept 4d2 and 4d3 using L. J. medium conventional method.

Conclusion: We developed an environmental friendly, high yield and mild condition protocol for the three-component Mannich-type reactions using EAN as ionic liquid. This method provided us several advantages by comparison with reported literature; which are as follows: (a) highly efficient catalyst activity, (b) ease of workable with green catalyst, (c) reaction proceeds without preparation of enol derivatives and pre-formed imines, (d) effective reusability of catalyst, making it a useful and attractive strategy. EAN was recovered and recycled four to five times without decreasing catalytic activity. Most of the compounds showed potential activities against Gram-positive bacteria rather than Chloramphenicol and Ciprofloxacin, accept 4d13. Compounds 4d3 to 4d12 were found to be more potent against C. Albicans and A. Niger rather than Nystatin and Griseofulvin. Antituberculosis activity of 4d8 to 4d12 compounds showed excellent activity rather than isoniazide against H37RV bacteria using L. J. medium conventional method.]]> <![CDATA[Tuberculosis Detection from Chest Radiographs: A Comprehensive Survey on Computer-Aided Diagnosis Techniques]]>https://www.eurekaselect.comarticle/86891

Discussion: The research on the development of CADx systems started four decades ago, and a large number of CADx systems have been developed till date. However, no independent survey focussing on the advancements in these systems has been presented. This paper fills this gap by consolidating the advancements and presents a comprehensive survey of CADx systems for TB detection developed till date with a focus on their underlying principles. It also discusses a practical model using which CADx systems can be used for screening TB in places where medical facilities and experts are not adequately available.

Conclusion: The paper also presents an overview of the current state of deep learning-based CADx systems. The development of these systems will remain in focus in the near future and will improve state-of-the-art performance in various medical domains.]]> <![CDATA[Ultra-Sensitive Electrochemical Sensor for the Determination of Pyrazinamide]]>https://www.eurekaselect.comarticle/83759

Pyrazinamide (PZM) is an antimycobacterial and a chief component of multidrug therapy for tuberculosis (TB). It is crucial for the prevention or treatment of TB infections. PZM has become an important component of short-term (6 months) multiple-drug therapy for tuberculosis. Owing to the high medical significance of PZM, it is necessary to develop a simple and rapid methodology for the analysis of PZM in various pharmaceutical is crucial. Ectrochemical methods with modified sensors have been exhibiting greater advantages in the current progressive scientific world. In the present manuscript a novel high sensitive electrochemical sensor was developed for the determination of PZM in various pharmaceutical samples. The developed sensor shows realistic behaviour towards pharmaceutical samples which is successfully monitored and tabulated in the present work.

Methodology: Voltammetric measurements were carried out with 797 VA Computrace system with version 1.3.1 software from Metrohm (Switzerland). PZM stock and standard solutions were made with 0.1 M phosphate buffer solution (PBS). The CuONPs were synthesized according to the previous report with slight modification. Electrode modification was performed in three different stages with MWCNTs, CuONPs and Cyt c to develop the finalized sensor. 10 ml of the PBS (pH 7) was introduced into the electrochemical cell. Thereafter a bare and modified GCE was dipped into the electrochemical cell followed by purging nitrogen gas for about 10 min and then the CV/DPV experiment was performed. An aliquot of the PZM solution was then introduced into the electrochemical cell, at 1000 rpm of rotating disc speed and the optimized pre-concentration potential was fixed for the voltammetric measurements. The cyclic and differential pulses voltammograms were monitored at the scan rate of 0.1 V s-1 with the potentials increasing towards the positive direction. In addition the real pharmaceutical samples were also analysed via standard addition method.

Results: Infrared spectroscopy and X-ray diffraction study characterization reveals the confirmation of formed CuONPs. Transmission electron microscopic studies confirmed the surface characterization of finalized sensor. Additionally, thermogravimetric analyses support the confirmation of the formed nanocomposite coated on the surface of GCE. Randles-Sevick equation reveals the high surface area of the modified sensor. This indicates the development of a suitable platform for electrochemical redox mechanism of PZM on the surface of the final sensor. The utmost electrochemical parameters like pH, scan rate, and deposition time were optimized. The developed sensor showed enhanced electrochemical sensing peak currents in cyclic voltammetry. The differential pulse voltammetry showed the linear range 3-30 µM with good LOD and LOQ of 0.0038 µM and 0.0129 µM respectively. The developed sensor showed good percentages of recovery viz., 99.5% and 98.2% respectively.

Conclusion: In the present work the developed sensor showed good catalytic activity towards PZM, due to the increased electrochemical sensing mechanism for PZM. The modified electrode was successfully characterized by the TEM, FT-IR, TGA and XRD techniques. The fabricated sensor showed enhanced peak currents and low detection limits with PZM. The proposed sensor showed excellent sensitivity, selectivity and low detection limits. In addition the developed sensor was applied for the determination of PZM in real pharmaceutical samples, and reflects good recovery percentages. It is evident that the proposed method will serve as a standard protocol for the determination of PZM in various pharmaceutical samples, and would be of great help to pharmaceutical industries in the future.]]> <![CDATA[Heterocyclic N-oxides - A Promising Class of Agents against Tuberculosis, Malaria and Neglected Tropical Diseases]]>https://www.eurekaselect.comarticle/89778 <![CDATA[Targeting the Folate Receptor: Improving Efficacy in Inorganic Medicinal Chemistry]]>https://www.eurekaselect.comarticle/88434 <![CDATA[Update on Nitazoxanide: A Multifunctional Chemotherapeutic Agent]]>https://www.eurekaselect.comarticle/85034

Method: Current review compiled the potential chemotherapeutic efficacy of NTZ against a variety of such disease-causing macro and/or micro-organisms as well as neoplastic cells, using various search engines viz. Web of Science, Scopus and Pub- Med up to February 2017.

Result: The most accepted anti-infective mechanism of NTZ involves impairment of the energy metabolism in anaerobic pathogens by inhibition of the pyruvate: ferredoxin/ flavodoxin oxidoreductase (PFOR). In parasitic-protozoan NTZ also induces lesions/voids in the cell membrane and depolarises the mitochondrial membrane along with the inhibition of quinone oxidoreductase NQO1, nitroreductase-1 and protein disulphide isomerase. NTZ also inhibits the glutathione-S-transferase (a major detoxifying enzyme) and modulates a gene (avr-14 gene) encoding for the alphatype subunit of glutamate-gated chloride ion channel present in the nematodes. Apart from well recognized non-competitive inhibition of the PFOR in anaerobic bacteria, NTZ also showed a variety of other antibacterial mechanisms viz. inhibits pyruvate dehydrogenase in the Escherichia coli, disrupts the membrane potential and pH homeostasis in the Mycobacterium tuberculosis, suppresses the chaperone/usher (CU) pathway of the gram-negative bacteria and stimulates host macrophage autophagy in the tubercular patients. NTZ also suppresses the viral replication by inhibiting maturation of the viral hemagglutinin and the viral transcription factor immediate early 2 (IE2) as well as by activating the eukaryotic translation initiation factor 2α (an antiviral intracellular protein). Additionally, NTZ expresses inhibitory effect on the tumour cell progression by modulating drug detoxification (glutathione-S-transferase P1), unfolded protein response, autophagy, anti-cytokines activities and c-Myc inhibition.

Conclusion: These potentially versatile molecular interactions of NTZ within invading pathogen(s) and immunomodulatory efficacy over the hosts, justify the multifunctional chemotherapeutic significance of this chemical agent.]]> <![CDATA[Exploring Promising Immunomodulatory Potential of Natural and Synthetic 1,3-Diphenyl-2-propen-1-one Analogs: A Review of Mechanistic Insight]]>https://www.eurekaselect.comarticle/87087 <![CDATA[Detection of the Incidence of Infections and Acute Biochemical Changes in Diffused Large B-Cell Lymphoma Patients Treated with Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP) with and without Rituximab]]>https://www.eurekaselect.comarticle/89225

Aims and Objectives: The objectives of our study were to determine the changes in biochemical disturbances induced by CHOP or RCHOP and second objective was to compare the effect of CHOP with or without rituximab on the incidence of the infections such as (Cytomegalovirus, Herpes Simplex Virus and Varicella-Zoster virus), bacterial infections and tuberculosis.

Materials and Methods: Files were prospectively reviewed during the tenure of 2014-2016. Participants aged greater than or equal to 18 years old with a known case of DLBCL undergoing CHOP or RCHOP chemotherapy were allowed to be included in the study. Baseline and posttreatment patients profile of blood chemistry, liver functions test was collected and compared with the Common Terminology Criteria for adverse events v3.0 2009 CTCAE 2009 and the data regarding infection of Cytomegalovirus, Herpes Simplex Virus and Vericella-Zoster virus, bacterial infections and tuberculosis were drawn from the participant's profile.

Results: Patients treated with CHOP therapy showed a significant difference of Alkaline Phosphatase (ALP) (p-value 0.009), direct bilirubin (p-value 0.034) and serum glutamic-pyruvic transaminase (SGPT) (p-value 0.004). Bacterial Pneumonia was only 1 (5%) and 1 (5%) CMV reported positive after the R-CHOP.

Conclusion: We propose that liver profile including (bilirubin, SGOT and SGPT) Urea, Creatinine and electrolytes should strictly be considered if found deranged before every treatment cycle and suspend chemotherapy in case of moderate or severe toxicity. ]]> <![CDATA[Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?]]>https://www.eurekaselect.comarticle/89346 <![CDATA[The Potential of Ganoderma Lucidum as Antimicrobial Agent for Multidrug- Resistant Mycobacterium Tuberculosis]]>https://www.eurekaselect.comarticle/88843 Methods: This study used a solid dilution method to test the extract of G. lucidum as an antibacterial agent.

Results and Conclusion: Results showed that all strains of multidrug-resistant tuberculosis (MDR-Tb) gave similar responses to G. lucidum extract at various concentrations. The bacteria did not grow on the medium containing G. lucidum extract at the smallest concentration of 12.5%, as well as concentrations of 25% and 50%. Ganoderma lucidum can be used as one of the alternatives for MDR-Tb drugs in the future.]]> <![CDATA[Editorial: Nanomedicines for the Treatment of Tuberculosis: Role of Nanocarriers and Functional Excipients]]>https://www.eurekaselect.comarticle/90172 <![CDATA[Nanoemulsion-Based Transdermal Drug Delivery System for the Treatment of Tuberculosis]]>https://www.eurekaselect.comarticle/83845 Methods: For nanoemulsions formulation, they have to deliver the energetic element at the specific organ with nominal uneasiness. Because of the prevention of hepatic first pass uptake transdermal course excel usual crest and trough plasma shape that usually comfort the administration. The antitubercular drugs relate to the formulation of Poly DL-Lactide-Co-Glycolide nanoparticles having an active substance encapsulated within and that the encapsulated substances are stable with respect to each other.

Conclusion: The present study aimed to explore the challenges and methods in order to increase the solubility of poorly aqueous soluble drug for improved bioavailability alongwith relative study of toxicity problems related to anti-tubercular drug. ]]> <![CDATA[New Drugs and Vaccines for Tuberculosis]]>https://www.eurekaselect.comarticle/86234 Methods: The dangerous combinations of TB and HIV is taking its toll on human health. The foremost factor is non- profit associated with the development of anti TB drugs. There is almost 10 different drugs in various levels of trials whereas the vaccine development is focusing more on adult vaccine rather than a child vaccine.

Results: More than 15 vaccine candidate are in various stages of pipelines. Present compilation gives an account for various drug candidates and vaccine products in various stages of drug development. Also included is a recent collection of patents for assay methods, potential drug candidates/classes and vaccination products.

Conclusion: The need is for improvement in the activity and chemical and biological description of under development compounds. Lastly the set up for clinical and appropriate uses for running a reliable clinical trial is a necessary prerequisite.]]> <![CDATA[Recent Complications and Issues in Tuberculosis Treatment]]>https://www.eurekaselect.comarticle/86232 Methods: Physicians conducted the interviews using a structured questionnaire. Information from the medical reports available at health care centers (especial results of sputum microscopy, radiological and other investigations) was also distracted. Patients is said to be infected with TB having a minimum two initial +ve sputum smears or one +ve sputum smear and chest radiographic abnormalities along with active pulmonary TB as determined by clinician; one sputum +ve culture specimen +ve for Mycobacterium tuberculosis. High resolution computed tomography (HRCT), a new susceptible technique shows erratically disseminated military nodules. The organs associated and extents of lesions of miliary TB in the pulmonary tuberculosis are examined by ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI). Histopathological examination of tissue biopsy is a conservative and fast technique for the separation of mycobacterium tuberculosis and assessment of choroid tubercles in fundus.

Conclusion: Even though numerous prognostic markers have been described which envisage mortality, yet untreated miliary TB has a serious outcome within one year. A high index of clinical research, early diagnosis and timely institution of anti-tuberculosis treatment can be life-saving. Response to first-line anti-tuberculosis drugs is good. Anti–tuberculosis drugs are patent.]]> <![CDATA[Nano-carriers for the Treatment of Tuberculosis]]>https://www.eurekaselect.comarticle/83075

Methods: There are numerous nano sized drug delivery systems like lipid nanoparticles, polymeric micelle, carbon nanotubes and polymeric nanoparticles that have been reported for a long time to treat diseases. There are a number of drawbacks in conventional TB dosage forms such as the development of multiple drug resistance, resulting in intolerable toxicity and high drug dose required. So, to overcome the drawbacks of conventional therapy, there is a need for a new drug delivery system with an aim to reduce the side effects of drug treatment. Nano-sized based drug delivery systems have considerable potential for the treatment of tuberculosis. These delivery systems have several advantages like high stability, high loading capacity, the feasibility of incorporation of both hydrophilic and hydrophobic drugs, and feasibility of variable routes of administration, and prolonged drug release from the matrix. These advantages enable enhanced drug solubility, bioavailability, reduced dosing frequency, high targeting, and may resolve the problem of non adherence to prescribed therapy, which is one of the major obstacles in the control of tuberculosis epidemics.

Conclusion: This article gives an exhaustive review of patents and research papers published over the years on the challenges, the current treatment therapy of the disease faces, and potential advantages of nano sized formulations to offer more effective treatment and prevention for tuberculosis.]]> <![CDATA[Nanoemulsion for the Effective Treatment and Management of Anti-tubercular Drug Therapy]]>https://www.eurekaselect.comarticle/83246

Methods: The conventional drug therapy employed for the treatment of tuberculosis is not highly satisfactorily owing to low oral bioavailability of the drugs. The evolution of nano-technology recently in few decades has completely revolutionized the treatment of diverse diseases and so is the tuberculosis. Nanotechnology not only possesses enormous potential for improving the biopharmaceutical performance, but also allows the delivery of therapeutic molecules to the desired site of action. Diverse types of nanocarriers have been employed for the treatment of tuberculosis infections. In this regard, nanoemulsions are considered as one of the promising alternatives for augmenting the bioavailability of the antitubercular drugs through oral route for improving their therapeutic efficacy.

Conclusion: The nanoemulsion loaded with antitubercular drugs can easily cross the biological barriers to reach the systemic circulation and consequently in the target for reducing the load of Mycobacterium tuberculosis. Besides, the lipidic nature of such systems facilitates targeting of the drugs to the lymph nodes, thus improves drug bioavailability and reduction of the dosing frequency. In lieu of this, the present article compiles the basics of nanoemulsions in brief along with an updated account on their applications in delivering antitubercular drugs for enhanced immunization. Moreover, overview of patent literature published in this area has also been included in the manuscript. ]]> <![CDATA[Macrophage Targeted Cellular Carriers for Effective Delivery of Anti-Tubercular Drugs]]>https://www.eurekaselect.comarticle/87307 Methods: One third of the world’s population is infected with TB. Recently it is estimated around 9.6 million people around the world became sick with TB disease. There were 1.5 million TB-related deaths worldwide. Therefore with the advent in biotechnology and Nano engineering, newly adapted survival molecular mechanism of Mycobacterium tuberculosis, new targets receptors on alveolar macrophages must be explored out for eradication of TB from the globe. Macrophage acts as a reservoir of phagocytic receptors to execute diverse physiological functions as well as to perform defense mechanism.

Results: Advances in novel carriers open new era for the treatment of tuberculosis which remains a very substantial global health encumbrance. Different binding receptors especially mannose, folate and scavenger receptors are attractive platform for internalization of therapeutics in alveolar macrophage. Nano-carriers and nano-devices designed after the acquaintance of receptor composition and functioning affords site specific targeting of biodegradable and biocompatible drug delivery systems for the treatment of tuberculosis offering complete cure and patient compliance.

Conclusion: This chapter encompasses recent studies on nanocarriers and new treatment strategies for tuberculosis. In spite of the budding benefits of nano carriers, many limitations still remain to be overcome such as poor oral stability, instability in circulation, inadequate tissue distribution as well as toxicity to normal cells.]]> <![CDATA[Nanostructured Therapeutic Carriers for Tuberculosis Treatment: Approaches & Challenges]]>https://www.eurekaselect.comarticle/86233 Methods: This review discusses the potential of nanomedicine and related patents to improve intracellular disease chemotherapy. To complete the objective, we searched bibliographic databases of indexed literature using a focused and structured criteria. The quality and characteristics of selected papers were assessed using standard parameters with qualitative analysis having a conceptual framework.

Results: Nanoparticle-based drug delivery systems are suitable for the treatment of illnesses, such as tuberculosis. Due to the unique size-dependent properties, nanocarriers such as nanoparticles, liposomes, niosomes and microspheres offer the opportunity to develop new therapeutic and diagnostic tools. The ability to integrate drugs into nanosystems displays a new standard in pharmacotherapy that could be used for cell-targeted drug therapy. Experimental data showed the possibility of intermittent chemotherapy with main antituberculosis drugs by employing nanocarriers. Besides the advantage of the controlled release of medications in organs, the other benefits of the nanocarriers include the possibility of various routes of therapy, reduction in drug dosage and adverse effects, reduced possibility of drug interactions, and drug-resistant targeting. Published literature including patented studies suggests that nanomedicine mediated drug delivery may improve tuberculosis chemotherapy by offering benefits such as targeting to the specific organs, sustained and controlled drug release, tuberculosis diagnosis, drug delivery to the pathogen’s intracellular location, and tuberculosis vaccine development.

Conclusion: The properties of nanomedicine may prove beneficial in developing improved, efficacious or alternative therapies for tuberculosis diseases. ]]> <![CDATA[Current Approaches and Future Prospects of Nanomedicine in Tuberculosis Therapy]]>https://www.eurekaselect.comarticle/83015 Objective: In recent years, an estimated of 9.6 million TB cases occurred and 1.5 million death occurred due to TB worldwide.

Conclusion: The present review is an attempt to introduce this disease focusing on the pathophysiology of the disease, the current approaches and the related patents for treatment and the future planning for combating this disease. ]]> <![CDATA[IL-10 Promoter -592 Polymorphism may Influence Susceptibility to HIV Infection in South Indian Population]]>https://www.eurekaselect.comarticle/88645

Objective: In this study, we studied IL-10 -592(C/A) and TGF-β -509 (C/T) promoter polymorphisms to understand their role in susceptibility or resistance to HIV and TB in a South Indian population.

Method: Genomic DNA was isolated from healthy controls, pulmonary tuberculosis patients (n=122) and HIV positive individuals (n=100) and used for genotyping by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) method.

Results: Results revealed that under dominant model (CC vs CA+AA), IL-10 -592 ‘A' allele either ‘CA' or ‘AA' combinations significantly associated with susceptibility to HIV compared to healthy controls (OR: 1.88(1.05-3.35); p=0.030). However, we found no significant association with TB. TGF-β -509 polymorphism did not associate with either HIV or TB under overdominant model. Neither of the promoter polymorphisms associated with sex in either HIV or TB. However, a trend towards higher risk to HIV was found in females compared with males in IL-10 -592 ‘AA' genotype.

Conclusion: This study suggests the association of IL-10 -592 “AA” genotype with susceptibility to HIV under dominant model in the Southern Indian population. Future studies are needed with a larger sample size in order to confirm the observations made in this study.]]> <![CDATA[Development and Validation of a Fast Reversed Phase Liquid Chromatographic Method for the Analysis of Ethionamide in Dosage Forms]]>https://www.eurekaselect.comarticle/85328

Methods: Chromatographic separation was achieved using a Hypersil BDS C18 (150 mm×4.6 mm, 3 µm) column kept at 30 °C. The mobile phase consisted of 300 mL of acetonitrile, 0.14 g of NH4H2PO4 and 700 mL of water pumped at a flow rate of 1.0 mL/min. UV detection was performed at 287 nm. The developed LC method was validated according to the ICH guidelines.

Results: Validation results show that the developed LC method is specific, linear, sensitive, precise, accurate and robust. Forced degradation studies revealed that the generated degradation products did not interfere with ETA and known impurities, thus proving the specificity of the developed LC method for the assay of ETA tablets and quantification of impurities.

Conclusion: A robust, selective, sensitive and fast LC method has been developed and validated for analysis of ETA and its main impurities in tablets.]]> <![CDATA[Vitamins Based Novel Target Pathways/Molecules as Possible Emerging Drug Targets for the Management of Tuberculosis]]>https://www.eurekaselect.comarticle/86662

Objective: The purpose of this review study was to describe vitamins as drug target that can be explored to develop new anti tubercular drugs that can treat both drug-sensitive and resistant TB infections.

Method: The methodological approaches include literature review which is performed in the databases like PubMed, Web of Science, Scopus, Springer and Science Direct, etc. On the basis of evaluation of literature sources, the review was complied.

Results: This review study demonstrated that vitamins biosynthesis pathway could be used in the development of novel drug targets. Further sequencing of the Mtb genome facilitated research in target identification and validation that make possible the discovery of novel anti-TB agent with new mechanisms of action. Several compounds were identified, which target vitamin biosynthesis pathway /enzymes. Some other new targets were also identified and can be explored for the identification of novel structural moiety.

Conclusion: Further exploration of these compounds which have been identified to target these vitamins related novel target pathways /molecules could led to the development of antitubercular drug which can be used in the treatment of drug sensitive and resistant TB.]]> <![CDATA[Preliminary Studies on Ligand-based Design and Evaluation of New Mycobacterial ATP Synthase Inhibitors]]>https://www.eurekaselect.comarticle/85675

Objective: Novel mycobacterial ATP synthase inhibitors having structural similarity with phenothiazines were designed in an attempt to develop potent antitubercular agents with no or less side effects.

Methods: The designed molecules were synthesized and screened against Mycobacterium tuberculosis H37Rv (Mtb). The compounds with strongest growth inhibition of whole Mtb (S3, S4, S9, S10, and S16) were screened for ATP synthesis inhibition using inverted membrane vesicles from Mycobacterium smegmatis, and were also screened for bloodbrain barrier (BBB) permeability and mammalian cell cytotoxicity to assess the possible side effects.

Results: Among all the compounds, S9 and S10 were found to be the most active (6.25 µg/mL) against Mtb and were comparable to chlorpromazine (12.5 µg/mL). Moreover, the compounds inhibited ATP synthesis at IC50 of 14 and 10.4 µM, respectively. A better correlation between MIC and IC50 observed, indicated that the compounds acted through mycobacterial ATP synthase inhibition. The blood-brain barrier (BBB) crossing ability of the compounds (S9, S10) was found to be less, indicating diminished CNS side effects. The compounds (S3, S4, S9, S10, and S16) were also marked safe against mammalian VERO cells, as CC50 was > 102 µg/mL.

Conclusion: The enhanced antitubercular activity with reduced BBB permeability exhibited by the compounds has good prospect to develop them as antitubercular drugs.]]> <![CDATA[Fracture Risk Associated with Use of Antibiotics]]>https://www.eurekaselect.comarticle/87187

Objectives: To study fracture risk associated with antibiotics.

Methods: It is a case control study. There were 124,655 fracture cases and 373,962 age and gender matched controls. The main exposure was use of various groups of antibiotics. Confounder control was performed for social variables, contacts to hospitals and general practitioners, alcoholism and a number of other variables.

Results: An increased risk of any fracture (OR =1.45, 95% CI: 1.42 -1.49), hip (1.46, 95% CI: 1.35- 1.58), forearm (1.67, 95% CI: 1.55 -1.80), and spine fractures (1.38, 95% CI: 1.18-1.60) was seen with the use of dicloxacillin and flucloxacillin. There was a dose response relationship for overall risk of fractures, hip, and forearm fractures but not for spine fractures with dicloxacillin and flucloxacillin. None of the other groups of antibiotics against bacteria, tuberculosis, virus, and fungi were systematically associated with any major change in the risk of fractures.

Conclusion: Dicloxacillin and flucloxacillin seem associated with an increased risk of fractures. The cause for this increase has to be determined but may be related to their use against infections of the bone, the increase thus rather being due to the underlying disease than the drug. Other types of antibiotics especially the fluoroquinolones were not systematically associated with an increased risk of fractures.]]>