Abstract: Background: Alternative and complementary applications of newly synthesized chemicals have enhanced the prospect of finding curative treatments for liver hepatocarcinogenesis and pancreatic cancer. Methods: The current study investigated the curative effect of the newly synthesized drug 4-methyl-N-((4-(trifluoromethoxy) phenyl) carbamoyl) benzenesulfonamide (3) against diethyl nitrosamine (DEN) (50 mg/kg) and carbon tetrachloride (CCl4) (2 mg/kg)-induced hepatocellular carcinoma (HCC) and pancreatic cancer in male rats using doxorubicin as a reference drug. Results: The results showed that treatment with DEN/CCl4 generated oxidative stress, as indicated by a rise in malondialdehyde (MDA) and a decrease in glutathione (GSH) levels. A meantime decrease in antioxidant, total antioxidant capacity (TAC) was detected. The study found that there was an increase in the levels of TNF-α and other inflammatory markers, interleukin-6 (IL-6) and B-cell lymphoma 2 (Bcl-2 ). Our findings revealed a considerable rise in hepatocellular carcinoma biomarkers α-fetoprotein and α-L-Fucosidase (α-FU) in the liver and pancreas. This was accompanied by alterations in the hepatic function biomarkers, which are characterized by higher levels of transaminases (AST, ALT), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT). Our findings were supported by immuno-histochemical and pathological examinations, which revealed considerable improvement in liver and pancreas tissues after treatment with medication 3 when compared to normal healthy rats. Conclusion: To summarize, the new synthetic medication 3 could be an effective chemotherapeutic method for treating DEN, CCl4-induced HCC, and pancreatic cancer.

Aim: Due to interdisciplinary research, many innovative concepts have been merged which seemed to be impractical. Recently medicinal organometallic chemistry has made remarkable progress but the latency of these compounds has not been fully exploited. This systematic Review examines the published literature on Anticancer organometallic chemistry across countries, science fields, and organizations involved in organometallics research for cancer. Methods: The study data related to Anticancer Organometallics was searched from Scopus between 2085 and 2022. Biblioshiny and VOS Viewers were used to analyze and visualize patterns in scientific literature derived from Scopus. Results: Publications on organometallic compounds used in the study, on average, 1.02% per year, making the last two decades since 2003, 94.3% of the total scholarly work published. However, research productivity has steadily improved, with 81.5% of all publications produced between 2011 and 2022. The countries possessing the highest published work were China, the UK, and Germany. The leading institutions, the University of Warwick, United Kingdom, and the University of Auckland, New Zealand, topped the list of organizations with the most publications. Although the use of medicinal organometallics for cancer has become widespread over the last two decennaries, there has been a notable influx of groundbreaking scientific publications in recent years. Conclusions: The findings of this study enable researchers to envision potential future scenarios for scientific collaborations involving the utilization of organometallics in the treatment of cancer. This study provides aspiring and current researchers with the necessary tools and knowledge to effectively pursue their research endeavors for scientific collaborations investigating the use of AOs in medicines. The areas, such as ruthenium with reactive oxygen species and angiogenesis, represent opportunities for future investigation and innovation.

Over expression of HDAC8 was observed in various cancers and inhibition of HDAC8 has emerged as a promising therapeutic approach in recent decades. To facilitate the discovery of novel selective HDAC8 inhibitors, in this review, diverse structural scaffolds of 66 known selective HDAC8 inhibitors were retrieved from literature with their IC50 values against HDAC8 and with other HDACs, clustered them based on their structural symmetry, identified common pharmacophores for each cluster using Phase, performed molecular docking with all HDACs to find out binding affinity and identified crucial interacting residues for HDAC8 inhibition. One representative of each cluster was subjected to molecular dynamic simulation to find out the range of RMSD of HDAC8 in HDAC8-ligand complexes, RMSF active site amino acid residues and identified crucial interacting amino acid residues responsible for HDAC8 inhibition. Active site amino acid information, active site cavities of all HDACs, and basic structure of Zn2+ binding group were also reviewed. The common pharmacophores AADHR_1, AADDR_1, ADDR_1, AADHR_1, ADHHR_1, ADHHR_1, and AADRR_1 were identified from different clusters of selective HDAC8 inhibitors. Molecular docking analysis identified the crucial interacting residues were HIS-142, GLY-151, HIS-143, PHE-152, PHE-20 in the main pocket and ARG-37, TYR-100, TYR-111, TYR-306 in the secondary pocket. The RMSD of protein and RMSF of active site amino acid residues for stable protein-ligand complexes should be less than 2.4 Å and 1.0 Å, respectively identified from MD trajectories. The range of Molecular Mechanics Generalized Born Surface Area (MM-GBSA) dG was predicted from MD trajectories lies between -15.8379Å− -61.5017Å kcal/mol. These findings may be used for rapid discovery of selective HDAC8 inhibitors.

The cancer disease has been a continuous threat globally. Several research for finding the best and most effective route for the cure of this disease. In this review, we tried to figure out the role of indole derivatives as Molecularly targeted anticancer therapy. The formation, advancement, and dissemination of a particular tumor are influenced by distinct molecular targets that are impacted by the indole analogs. Unlike conventional chemotherapeutics, which act cytotoxically, target anticancer drugs act cytostatically and are usually designed to achieve certain objectives. Anticancer medications currently in use target the receptor proteins known as vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and Fms-like tyrosine kinase 3 (FLT3), tropomyosin receptor kinase (TRK) inhibitors, Abelson murine leukemia 1 (ABL1) inhibitors, Bruton's agammaglobulinemia tyrosine kinase (BTK) inhibitors, BRAF Inhibitors, Cyclin-dependent kinases inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, BCL 2 inhibitors, and PARP inhibitors. All these receptors are targeted by the various indole analogs to find effective medication for the cancer. This review also relates to the structural relation (SAR) with the various indole analogs having anticancer activity.

One of the actively developing areas of drug development is the creation of chimeric toxins, recombinant bifunctional molecules designed to selectively affect target cells. The prevalent approach involves fusing bacterial and plant toxins with molecules that facilitate targeted delivery. However, the therapeutic use of such toxins often encounters challenges associated with negative side effects. Concurrently, viruses encode proteins possessing toxin-like properties, exerting multiple effects on the vital activity of cells. In contrast to bacterial and plant toxins, the impact of viral proteins is typically milder, presenting a significant advantage by potentially reducing the likelihood of side effects. This review delineates the characteristics of extensively studied viral proteins with toxic and immunomodulatory properties and explores the prospects of incorporating them into chimeric toxins.