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
-
Central Nervous System Agents for Ischemic Stroke: Neuroprotection Mechanisms
Central Nervous System Agents in Medicinal Chemistry Maternal Immunomodulation Therapy for Prevention of Preterm Birth and Prematurity-Related Morbidity: The New Era of Immuno-Perinatology
Current Pharmaceutical Design Genetic Alterations in Differentiated Thyroid Cancers
Endocrine, Metabolic & Immune Disorders - Drug Targets Role of Matrix Metalloproteinases in Animal Models of Ischemic Stroke
Current Vascular Pharmacology Gene Therapy of Cancer with Interleukin-12
Current Pharmaceutical Design Editorial: Medical Science Beyond Formal Institutional Boundaries
Inflammation & Allergy - Drug Targets (Discontinued) Inhibitors of the Metalloproteinase Anthrax Lethal Factor
Current Topics in Medicinal Chemistry Epidermal Growth Factor Receptor-Targeted Therapy of Colorectal Cancer with Panitumumab
Current Cancer Therapy Reviews Nitrosative Stress During Infection-Induced Inflammation in Fish: Lessons From a Host-Parasite Infection Model
Current Pharmaceutical Design Therapeutic Agents for COVID-19: an Overview
Current Drug Therapy Clinical Trials for Acute Kidney Injury: Design Challenges and Possible Solutions
Current Drug Targets Neuromyelitis Optica (NMO IgG+) and Genetic Susceptibility, Potential Ethnic Influences
Central Nervous System Agents in Medicinal Chemistry Recent Patents Therapeutic Agents for Cancer
Recent Patents on Anti-Cancer Drug Discovery Novel Rational Drug Design Strategies with Potential to Revolutionize Malaria Chemotherapy
Current Medicinal Chemistry Design, Synthesis, Characterization, QSAR, Docking, Anti-inflammatory and Analgesic Evaluation of Some New Phthalazinediones
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry A Review of the Diagnosis and Treatment of Necrotizing Enterocolitis
Current Pediatric Reviews Effects of Antiretroviral Therapy on Immunity in Patients Infected with HIV
Current Pharmaceutical Design Improved Brain Expression of Anti-Amyloid β scFv by Complexation of mRNA Including a Secretion Sequence with PEG-based Block Catiomer
Current Alzheimer Research Biologic Therapy and Treatment Options in Diabetic Retinopathy with Diabetic Macular Edema
Current Drug Safety Resident Kidney Cells and Their Involvement in Glomerulonephritis
Current Drug Targets - Inflammation & Allergy