Abstract
Migrastatin, a macrolide natural product, and its structurally related analogs are potent inhibitors of cancer cell metastasis, invasion and migration. In the present work, a specialized fragment-based method was employed to develop QSAR models for a series of migrastatin and isomigrastatin analogs. Significant correlation coefficients were obtained (best model, q2 = 0.76 and r2 = 0.91) indicating that the QSAR models possess high internal consistency. The best model was then used to predict the potency of an external test set, and the predicted values were in good agreement with the experimental results (R2pred = 0.85). The final model and the corresponding contribution maps, combined with molecular modeling studies, provided important insights into the key structural features for the anticancer activity of this family of synthetic compounds based on natural products.
Keywords: Cancer, metastasis, QSAR, drug design, migrastatin, macrolide, inhibitors, invasion, migration, isomigrastatin analogs, correlation coefficients, anticancer activity
Medicinal Chemistry
Title: Quantitative Structure-Activity Studies on a Series of Migrastatin Analogs as Inhibitors of Cancer Cell Metastasis
Volume: 7 Issue: 3
Author(s): Ricardo N. Santos, Rafael V. C. Guido, Glaucius Oliva, Luiz C. Dias and Adriano D. Andricopulo
Affiliation:
Keywords: Cancer, metastasis, QSAR, drug design, migrastatin, macrolide, inhibitors, invasion, migration, isomigrastatin analogs, correlation coefficients, anticancer activity
Abstract: Migrastatin, a macrolide natural product, and its structurally related analogs are potent inhibitors of cancer cell metastasis, invasion and migration. In the present work, a specialized fragment-based method was employed to develop QSAR models for a series of migrastatin and isomigrastatin analogs. Significant correlation coefficients were obtained (best model, q2 = 0.76 and r2 = 0.91) indicating that the QSAR models possess high internal consistency. The best model was then used to predict the potency of an external test set, and the predicted values were in good agreement with the experimental results (R2pred = 0.85). The final model and the corresponding contribution maps, combined with molecular modeling studies, provided important insights into the key structural features for the anticancer activity of this family of synthetic compounds based on natural products.
Export Options
About this article
Cite this article as:
N. Santos Ricardo, V. C. Guido Rafael, Oliva Glaucius, C. Dias Luiz and D. Andricopulo Adriano, Quantitative Structure-Activity Studies on a Series of Migrastatin Analogs as Inhibitors of Cancer Cell Metastasis, Medicinal Chemistry 2011; 7 (3) . https://dx.doi.org/10.2174/157340611795564240
DOI https://dx.doi.org/10.2174/157340611795564240 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Cancer Stem Cells and the Tumor Microenvironment: Soloists or Choral Singers
Current Pharmaceutical Biotechnology Construction of a γ-Butyrolactone Moiety: A Facile Synthesis of 3β- Hydroxy-5,6-Dihydro-17β -Methoxy-Pregnan-21,16α-Carbalactone - a New D-Ring Fused Steroidal γ-Butyrolactone from an Abundant 20- Oxopregnane using Metal Mediated Halogenation as the Key Step
Letters in Organic Chemistry Osteoclast Apoptosis in Rheumatic Diseases Characterized by a High Level of Bone Resorption (Osteoporosis, Rheumatoid Arthritis, Myeloma and Pagets Disease of Bone)
Current Rheumatology Reviews Molecular Modelling, Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives for the Treatment of Breast Cancer
Current Chinese Chemistry Persistent GP130/STAT3 Signaling Contributes to the Resistance of Doxorubicin, Cisplatin, and MEK Inhibitor in Human Rhabdomyosarcoma Cells
Current Cancer Drug Targets Organ- and Cell-Type Specific Delivery of Kinase Inhibitors: A Novel Approach in the Development of Targeted Drugs
Current Molecular Pharmacology Current Trends in Cancer Biomarker Discovery Using Urinary Metabolomics: Achievements and New Challenges
Current Medicinal Chemistry Nanoparticles: Properties and Applications in Cancer Immunotherapy
Current Pharmaceutical Design Metabolism of Flavonoids in Human: A Comprehensive Review
Current Drug Metabolism Chemotherapy and Targeted Agents for Elderly Women with Advanced Breast Cancer
Recent Patents on Anti-Cancer Drug Discovery Targeting Heat Shock Proteins 70/90 and Proteasome for Cancer Therapy
Current Medicinal Chemistry Multimerization Improves Targeting of Peptide Radio-Pharmaceuticals
Current Pharmaceutical Design Magnetic Resonance Imaging of the Cervix, and its Relevance to the Revised International Federation of Gynecology and Obstetrics (FIGO) Staging
Current Medical Imaging Adipocytes Contribute to Resistance of Human Melanoma Cells to Chemotherapy and Targeted Therapy
Current Medicinal Chemistry Vitamin D Analogs- Drug Design Based on Proteins Involved in Vitamin D Signal Transduction
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Analysis of Oxaliplatin Resistance in Colorectal Cancer Cells by Combined Proteomics and Phosphoproteomic
Current Proteomics Emerging Trends in Endometriosis Treatment - Review
Current Women`s Health Reviews Editorial: Advances in the Treatment of Neurodegenerative Diseases and Epilepsy
Current Pharmaceutical Design Trifluoroibuprofen Inhibits α-Methylacyl Coenzyme A Racemase (AMACR/P504S), Reduces Cancer Cell Proliferation and Inhibits in vivo Tumor Growth in Aggressive Prostate Cancer Models
Anti-Cancer Agents in Medicinal Chemistry Hydrogen Sulphide: Biopharmacological Roles in the Cardiovascular System and Pharmaceutical Perspectives
Current Medicinal Chemistry