Abstract
An in-house library of 200 molecules from natural plant products was designed in order to evaluate their binding to Plasmodium ACP enoyl reductase (ENR), a promising biological target for antimalarial chemotherapeutics. The binding site of PfENR was explored computationally and the molecules were docked using AutoDock. Furthermore, the top-ranked scaffolds from docking studies were also compared with known PfENR inhibitors using 3D-QSAR. To this effect, a 3D-QSAR model was derived from a set of experimentally established PfENR inhibitors, using Comparative Molecular Force Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The best optimum CoMFA model exhibited a leave-one-out correlation coefficient (q2) and a noncross- validated correlation coefficient (r2) of 0.630 and 0.911, respectively. The result of this cumulative approach proposed five structurally distinct natural products as potent PfENR inhibitors. This study may lay a stepping stone towards Functional oriented synthesis (FOS) of novel PfENR inhibitors in future.
Keywords: Malaria, Plasmodium ACP enoylreductase (FabI), Molecular docking, CoMFA analysis, drug design.
Current Computer-Aided Drug Design
Title:Combined 3D-QSAR and molecular docking study for identification of diverse natural products as potent Pf ENR inhibitors
Volume: 11 Issue: 3
Author(s): Preeti Wadhwa, Debasmita Saha and Anuj Sharma
Affiliation:
Keywords: Malaria, Plasmodium ACP enoylreductase (FabI), Molecular docking, CoMFA analysis, drug design.
Abstract: An in-house library of 200 molecules from natural plant products was designed in order to evaluate their binding to Plasmodium ACP enoyl reductase (ENR), a promising biological target for antimalarial chemotherapeutics. The binding site of PfENR was explored computationally and the molecules were docked using AutoDock. Furthermore, the top-ranked scaffolds from docking studies were also compared with known PfENR inhibitors using 3D-QSAR. To this effect, a 3D-QSAR model was derived from a set of experimentally established PfENR inhibitors, using Comparative Molecular Force Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The best optimum CoMFA model exhibited a leave-one-out correlation coefficient (q2) and a noncross- validated correlation coefficient (r2) of 0.630 and 0.911, respectively. The result of this cumulative approach proposed five structurally distinct natural products as potent PfENR inhibitors. This study may lay a stepping stone towards Functional oriented synthesis (FOS) of novel PfENR inhibitors in future.
Export Options
About this article
Cite this article as:
Wadhwa Preeti, Saha Debasmita and Sharma Anuj, Combined 3D-QSAR and molecular docking study for identification of diverse natural products as potent Pf ENR inhibitors, Current Computer-Aided Drug Design 2015; 11 (3) . https://dx.doi.org/10.2174/1573409911666151030102113
DOI https://dx.doi.org/10.2174/1573409911666151030102113 |
Print ISSN 1573-4099 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6697 |
- 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
-
Fragment-Based Drug Discovery and Molecular Docking in Drug Design
Current Pharmaceutical Biotechnology Protein Tagging, Destruction and Infection
Current Protein & Peptide Science Pharmacogenetics and Inflammatory Bowel Disease
Current Pharmacogenomics and Personalized Medicine Pharmacological Therapy of Pericardial Diseases
Current Pharmaceutical Design The Role of Electrospinning in the Emerging Field of Nanomedicine
Current Pharmaceutical Design New Insights into Invasive Aspergillosis - from the Pathogen to the Disease
Current Pharmaceutical Design General Aspects of Two-Component Regulatory Circuits in Bacteria: Domains, Signals and Roles
Current Protein & Peptide Science Computational Biology and Drug Discovery: From Single-Target to Network Drugs
Current Bioinformatics Synthesis and Evaluation of Antimicrobial Activity of Thiazolidinone Derivatives
Letters in Drug Design & Discovery Peroxiredons: Tryparedoxin Peroxidase from Leishmania major
Current Regenerative Medicine (Discontinued) Optimizing Tumor-Reactive γδT Cells for Antibody-Based Cancer Immunotherapy
Current Molecular Medicine Phytochemical and Biological Activities of an Anticancer Plant Medicine: Brucea javanica
Anti-Cancer Agents in Medicinal Chemistry Glycine Rich P-loop Motif in Deoxyuridine Pyrophosphatase
Current Protein & Peptide Science Targeting IL-17 and IL-23 in Immune Mediated Renal Disease
Current Medicinal Chemistry Targeted Drug Delivery Systems for Lung Macrophages
Current Drug Targets Targeting TNF-Alpha in HIV-1 Infection
Current Drug Targets Synthesis and Antimicrobial Activity of Adamantyl Substituted Pyridoxine Derivatives
Letters in Drug Design & Discovery Antimycobacterial Assessment and Microwave-assisted Synthesis of 2-aryl- 3-(4-methylphenylamino)thiazolidin-4-one Derivatives
Letters in Organic Chemistry Is Renalase a Novel Player in Catecholaminergic Signaling? The Mystery of the Catalytic Activity of an Intriguing New Flavoenzyme
Current Pharmaceutical Design Quinoline – a Promising Fragment in the Search for New Antimalarials
Mini-Reviews in Medicinal Chemistry