Abstract
Among neutral endopeptidase (NEP) inhibitors, mercaptoacyldipeptides implicated in cardiovascular diseases, are of great interest. Two groups, Coric et al. and Oefner et al. described two different binding preferences for mercaptoacyldipeptides at the active site of NEP. By focusing on both, 3D-QSAR studies were performed on mercaptoacyldipeptides, based on conformational alignment obtained by GOLD 3.2, using CoMFA and CoMSIA techniques. Statistically significant 3D-QSAR models were obtained with q2 of 0.580 and 0.559, and r2 of 0.996 and 0.991, respectively. Both the models were validated by an external test set of nine compounds giving highly predictive r2 (pred) of 0.929 and 0.928, respectively. The study will facilitate the rational design of more potent mercaptoacyldipeptides for the treatment of cardiovascular diseases.
Keywords: Comparative molecular field analysis, comparative molecular similarity analysis, mercaptoacyldipeptides, neutral endopeptidase
Medicinal Chemistry
Title: Receptor-Based 3D-QSAR Study for Recognizing True Binding Mode of Mercaptoacyldipeptides at the Active Site of Neutral Endopeptidase
Volume: 5 Issue: 1
Author(s): Zaheer-ul-Haq and Sadaf Iqbal
Affiliation:
Keywords: Comparative molecular field analysis, comparative molecular similarity analysis, mercaptoacyldipeptides, neutral endopeptidase
Abstract: Among neutral endopeptidase (NEP) inhibitors, mercaptoacyldipeptides implicated in cardiovascular diseases, are of great interest. Two groups, Coric et al. and Oefner et al. described two different binding preferences for mercaptoacyldipeptides at the active site of NEP. By focusing on both, 3D-QSAR studies were performed on mercaptoacyldipeptides, based on conformational alignment obtained by GOLD 3.2, using CoMFA and CoMSIA techniques. Statistically significant 3D-QSAR models were obtained with q2 of 0.580 and 0.559, and r2 of 0.996 and 0.991, respectively. Both the models were validated by an external test set of nine compounds giving highly predictive r2 (pred) of 0.929 and 0.928, respectively. The study will facilitate the rational design of more potent mercaptoacyldipeptides for the treatment of cardiovascular diseases.
Export Options
About this article
Cite this article as:
Zaheer-ul-Haq and Iqbal Sadaf, Receptor-Based 3D-QSAR Study for Recognizing True Binding Mode of Mercaptoacyldipeptides at the Active Site of Neutral Endopeptidase, Medicinal Chemistry 2009; 5 (1) . https://dx.doi.org/10.2174/157340609787049253
DOI https://dx.doi.org/10.2174/157340609787049253 |
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
-
Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer’s Disease: Results from a Double-Blind, Placebo-Controlled Trial
Current Alzheimer Research Acute Antithrombotic Treatment of Ischemic Stroke
Current Vascular Pharmacology Electroconvulsive Therapy in Child and Adolescent Psychiatry
Current Psychiatry Reviews Sex Steroid Hormones, Cardiovascular Diseases and The Metabolic Syndrome
Cardiovascular & Hematological Agents in Medicinal Chemistry T-type Calcium Channels in Health and Disease
Current Medicinal Chemistry A Palliative Care Approach to the Advanced Heart Failure Patient
Current Cardiology Reviews Does Oral Metoprolol have Any Effect on the Functional Parameters and Perfusion Defects of the Left Ventricle?
Current Medical Imaging Pathomechanisms of Myocardial Dysfunction in Sepsis
Endocrine, Metabolic & Immune Disorders - Drug Targets Impact of Delayed Whole Blood Processing Time on Plasma Levels of miR- 1 and miR-423-5p up to 24 Hours
MicroRNA Statins and Vulnerable Plaque
Current Pharmaceutical Design Molecular and Biochemical Changes of the Cardiovascular System due to Smoking Exposure
Current Pharmaceutical Design Inhibition of Sumoylation Alleviates Oxidative Stress-induced Retinal Pigment Epithelial Cell Senescence and Represses Proinflammatory Gene Expression
Current Molecular Medicine Experimental Animal Models of Myocardial Damage in Regenerative Medicine Studies Involving Adult Bone Marrow Derived Stem Cells: Ethical and Methodological Implications
Cardiovascular & Hematological Disorders-Drug Targets The Retinal Pigment Epithelium in Health and Disease
Current Molecular Medicine Mitochondrial Tolerance to Drugs and Toxic Agents in Ageing and Disease
Current Drug Targets Congestive Heart Failure and Thyroid Dysfunction: The Role of the Low T3 Syndrome and Therapeutic Aspects
Endocrine, Metabolic & Immune Disorders - Drug Targets Depression and its Relation with Uncontrolled Hypertension and Increased Cardiovascular Risk
Current Hypertension Reviews Developments in Synthesis of the Anti-inflammatory Drug, Celecoxib: A Review
Recent Patents on Inflammation & Allergy Drug Discovery High Throughput Screening for Colorectal Cancer Specific Compounds
Combinatorial Chemistry & High Throughput Screening Renoprotective Potency of Heme Oxygenase-1 Induction in Rat Renal Ischemia-Reperfusion
Inflammation & Allergy - Drug Targets (Discontinued)