Abstract
Molecular modeling (MM) study is performed for Pipecolic acid based derivatives (PSAs) of tumor necrosis factor-α converting enzyme (TACE) inhibitors because of their very high selectivity for TACE over MMP-1. MM study was carried out by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular field Similarity Indices Analysis (CoMSIA) approaches. Computational docking simulations have also been performed to explore atomic details of TACE/PSA interactions and to identify the most important structural features of PSAs vital for TACE inhibitory activity. Molecular modeling study was performed using probable bioactive conformations, generated employing docking, for molecular alignment. The CoMSIA model resulted to be more predictive than CoMFA model, and gave conventional r2 0.996, r2cv 0.765, q2 0.783, SEE 0.025, F-value 472.149, r2boot 0.999 and r2test 0.788. Generated 3D-QSAR field contributions (contour maps) and results of docking analysis showed good correlation. Therefore, present studies will be useful for designing new molecules with improved TACE inhibitory activity in future.
Keywords: TACE inhibitors, Rheumatoid arthritis, CoMFA, CoMSIA, Docking, Converting Enzyme, Pipecolic Acid, TNF, necrosis, PSA, 3D-QSAR, cytokine, metalloproteinases, fusion
Letters in Drug Design & Discovery
Title: CoMFA and CoMSIA Analyses of Highly Selective Pipecolic Acid Based TNF-α Converting Enzyme (TACE) Inhibitors Using Docked Conformations for Molecular Alignment
Volume: 8 Issue: 5
Author(s): Malkeet Singh Bahia, Sukhvir Chand, Shravan Kumar Gunda, Shwetha Reddy Gade, Saikh Mahmood and Om Silakari
Affiliation:
Keywords: TACE inhibitors, Rheumatoid arthritis, CoMFA, CoMSIA, Docking, Converting Enzyme, Pipecolic Acid, TNF, necrosis, PSA, 3D-QSAR, cytokine, metalloproteinases, fusion
Abstract: Molecular modeling (MM) study is performed for Pipecolic acid based derivatives (PSAs) of tumor necrosis factor-α converting enzyme (TACE) inhibitors because of their very high selectivity for TACE over MMP-1. MM study was carried out by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular field Similarity Indices Analysis (CoMSIA) approaches. Computational docking simulations have also been performed to explore atomic details of TACE/PSA interactions and to identify the most important structural features of PSAs vital for TACE inhibitory activity. Molecular modeling study was performed using probable bioactive conformations, generated employing docking, for molecular alignment. The CoMSIA model resulted to be more predictive than CoMFA model, and gave conventional r2 0.996, r2cv 0.765, q2 0.783, SEE 0.025, F-value 472.149, r2boot 0.999 and r2test 0.788. Generated 3D-QSAR field contributions (contour maps) and results of docking analysis showed good correlation. Therefore, present studies will be useful for designing new molecules with improved TACE inhibitory activity in future.
Export Options
About this article
Cite this article as:
Singh Bahia Malkeet, Chand Sukhvir, Kumar Gunda Shravan, Reddy Gade Shwetha, Mahmood Saikh and Silakari Om, CoMFA and CoMSIA Analyses of Highly Selective Pipecolic Acid Based TNF-α Converting Enzyme (TACE) Inhibitors Using Docked Conformations for Molecular Alignment, Letters in Drug Design & Discovery 2011; 8 (5) . https://dx.doi.org/10.2174/157018011795514195
DOI https://dx.doi.org/10.2174/157018011795514195 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- 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
-
Bioactive Hydrogel Scaffolds - Advances in Cartilage Regeneration Through Controlled Drug Delivery
Current Pharmaceutical Design Liver-Related Factors Associated with Low Vitamin D Levels in HIV and HIV/HCV Coinfected Patients and Comparison to General Population
Current HIV Research Discovery of Highly Selective Inhibitors of p38α
Current Topics in Medicinal Chemistry Prevention and Management of Ovarian Hyperstimulation Syndrome
Current Women`s Health Reviews Lifestyle Modification in Rheumatoid Arthritis: Dietary and Physical Activity Recommendations Based on Evidence
Current Rheumatology Reviews High-level Soluble Expression, Purification, and Functional Characterization of the Recombinant Human Leukemia Inhibitory Factor: A Potential General Strategy for the Recombinant Expression of Cytokines Consisting of Four α-Helices in a Bundle
Protein & Peptide Letters Potential of Anti-inflammatory Molecules in the Chemoprevention of Breast Cancer
Recent Advances in Inflammation & Allergy Drug Discovery An Updated Review of Natural Products Intended to Prevent or Treat Oral Mucositis in Patients Undergoing Radio-Chemotherapy
Current Pharmaceutical Biotechnology Recent Patents on Influenza Vaccines
Recent Patents on Biotechnology The Role of Nitro (NO<sub>2</sub>-), Chloro (Cl), and Fluoro (F) Substitution in the Design of Antileishmanial and Antichagasic Compounds
Current Drug Targets Cardiovascular Risk in Rheumatoid Arthritis and Mechanistic Links: From Pathophysiology to Treatment
Current Vascular Pharmacology CD8<sup>+</sup> T Cell Responses to Plasmodium and Intracellular Parasites
Current Immunology Reviews (Discontinued) Bicyclol: A Novel Drug for Treating Chronic Viral Hepatitis B and C
Medicinal Chemistry Moderate Hyperhomocysteinemia and Immune Activation
Current Pharmaceutical Biotechnology Endothelial Dysfunction in Morbid Obesity
Current Pharmaceutical Design Blocking HIV-1 Replication by Targeting the Tat-Hijacked Transcriptional Machinery
Current Pharmaceutical Design Recent Developments in the Discovery of Selective Glucocorticoid Receptor Modulators (SGRMs)
Current Topics in Medicinal Chemistry New Insights into the Regulation of Liver Inflammation and Oxidative Stress
Mini-Reviews in Medicinal Chemistry Prognostic Value of Copeptin in Chronic Kidney Disease: From General Population to End-Stage Renal Disease
Current Protein & Peptide Science DNA Drug Design for Cancer Therapy
Current Pharmaceutical Design