Abstract
Melanoma is the fatal form of skin cancer. Herein, a three-dimensional quantitative structure-activity relationship study on a series of 105 colchicine binding site-targeted 2-arylthiazolidine-4-carboxylic acid amides (ATCAA) derivatives as melanoma antagonists was conducted. The optimal CoMSIA model yields a Q2 of 0.556, R2 ncv of 0.833 and R2 pred of 0.757, while the CoMFA yields a Q2 of 0.569, R2 ncv of 0.812 and R2 pred of 0.589. In addition, molecular docking was also carried out. The study results demonstrated that: (1) Bulky substituents in Rings C and D significantly increase the biological activity of compounds while decrease the activity at Rings A and B; (2) Electropositive groups at Rings A and B as well as electronegative groups at Ring C help to increase the activity; (3) HB donor favors Rings A and D while HB acceptor favors Rings B and C. Besides, a statistical analysis of the key amino acids as well as the ones forming HB with various antagonists of the colchicine binding site was conducted based on 34 essays and found HB to be the key interaction that MTAs have with the colchicine binding site and that Ala 250, Asn 258, Thr 179, Lys 254 and Lys 352 are vital in the composition of the site and the formation of HB. The results of this study provide useful information on designing antagonists with improved activity and insight on the composition of the colchicine binding site.
Keywords: 3D-QSAR, colchicine binding site, docking, melanoma cancer antagonists.
Medicinal Chemistry
Title:Structural Analysis for Colchicine Binding Site-Targeted ATCAA Derivatives as Melanoma Antagonists
Volume: 10 Issue: 3
Author(s): Jiawei Zhang, Feng Li, Yan Li, Yangyang Guo, Jinghui Wang and Shuwei Zhang
Affiliation:
Keywords: 3D-QSAR, colchicine binding site, docking, melanoma cancer antagonists.
Abstract: Melanoma is the fatal form of skin cancer. Herein, a three-dimensional quantitative structure-activity relationship study on a series of 105 colchicine binding site-targeted 2-arylthiazolidine-4-carboxylic acid amides (ATCAA) derivatives as melanoma antagonists was conducted. The optimal CoMSIA model yields a Q2 of 0.556, R2 ncv of 0.833 and R2 pred of 0.757, while the CoMFA yields a Q2 of 0.569, R2 ncv of 0.812 and R2 pred of 0.589. In addition, molecular docking was also carried out. The study results demonstrated that: (1) Bulky substituents in Rings C and D significantly increase the biological activity of compounds while decrease the activity at Rings A and B; (2) Electropositive groups at Rings A and B as well as electronegative groups at Ring C help to increase the activity; (3) HB donor favors Rings A and D while HB acceptor favors Rings B and C. Besides, a statistical analysis of the key amino acids as well as the ones forming HB with various antagonists of the colchicine binding site was conducted based on 34 essays and found HB to be the key interaction that MTAs have with the colchicine binding site and that Ala 250, Asn 258, Thr 179, Lys 254 and Lys 352 are vital in the composition of the site and the formation of HB. The results of this study provide useful information on designing antagonists with improved activity and insight on the composition of the colchicine binding site.
Export Options
About this article
Cite this article as:
Zhang Jiawei, Li Feng, Li Yan, Guo Yangyang, Wang Jinghui and Zhang Shuwei, Structural Analysis for Colchicine Binding Site-Targeted ATCAA Derivatives as Melanoma Antagonists, Medicinal Chemistry 2014; 10 (3) . https://dx.doi.org/10.2174/157340641003140304144930
DOI https://dx.doi.org/10.2174/157340641003140304144930 |
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
-
Electroporation in DNA Vaccination Protocols Against Cancer
Current Drug Metabolism Synthesis and Antiproliferative Effects of 5,6-Disubstituted Pyridazin-3(2H)-ones Designed as Conformationally Constrained Combretastatin A-4 Analogues
Anti-Cancer Agents in Medicinal Chemistry The Interaction of NK Cells and Dendritic Cells in the Tumor Environment: How to Enforce NK Cell & DC Action Under Immunosuppressive Conditions?
Current Medicinal Chemistry MICA Molecules in Disease and Transplantation, a Double-Edged Sword?
Current Immunology Reviews (Discontinued) Beyond Hemostasis: The Role of Platelets in Inflammation, Malignancy and Infection
Cardiovascular & Hematological Disorders-Drug Targets Melatonin, a Potential Therapeutic Agent for Smooth Muscle-Related Pathological Conditions and Aging
Current Medicinal Chemistry Manipulation of Glycolysis in Malignant Tumors: Fantasy or Therapy?
Current Medicinal Chemistry Anticancer Compounds as Leishmanicidal Drugs: Challenges in Chemotherapy and Future Perspectives
Current Medicinal Chemistry Cutaneous Melanoma: Fishing with Chips
Current Molecular Medicine Drug Targeting Strategies for Photodynamic Therapy
Anti-Cancer Agents in Medicinal Chemistry Detection of Tumor Markers with ProteinChip® Technology
Current Pharmaceutical Biotechnology New Peptidic GnRH Antagonists Offer a Broad Range of Therapeutic Applications
Letters in Drug Design & Discovery Medicinal Plants from Peru: A Review of Plants as Potential Agents Against Cancer
Anti-Cancer Agents in Medicinal Chemistry The Holy Grail of Polymer Therapeutics for Cancer Therapy: An Overview on the Pharmacokinetics and Bio Distribution
Current Drug Metabolism Use of Fullerenes in Cosmetics
Recent Patents on Biotechnology Nanocarriers Conjugated with Cell Penetrating Peptides: New Trojan Horses by Modern Ulysses
Current Pharmaceutical Biotechnology Prophylactic Vaccine Approach for Colon and Pancreatic Cancers: Present and Future
Current Medicinal Chemistry CD36 as a Multiple-Ligand Signaling Receptor in Atherothrombosis
Cardiovascular & Hematological Agents in Medicinal Chemistry Current and Experimental Antibody-Based Therapeutics: Insights, Breakthroughs, Setbacks and Future Directions
Current Molecular Medicine Agonists and Antagonists of Protease Activated Receptors (PARs)
Current Medicinal Chemistry