Document Detail


Identification of novel antitubercular compounds through hybrid virtual screening approach.
MedLine Citation:
PMID:  20727773     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Growing resistance of prevalent antitubercular (antiTB) agents in clinical isolates of Mycobacterium tuberculosis (MTB) provoked an urgent need to discover novel antiTB agents. Enoyl acyl carrier protein (ACP) reductase (InhA) from Mtb is a well known and thoroughly studied as antitubucular therapy target. Here we have reported the discovery of potent antiTB agents through ligand and structure based approaches using computational tools. Initially compounds with more than 0.500 Tanimoto similarity coefficient index using functional class fingerprints (FCFP_4) to the reference chemotype were mined from the chemdiv database. Further, the molecular docking was performed to select the compounds on the basis of their binding energies, binding modes, and tendencies to form reasonable interactions with InhA (PDB ID=2NSD) protein. Eighty compounds were evaluated for antitubercular activity against H37RV M. tuberculosis strain, out of which one compound showed MIC of 5.70 microM and another showed MIC of 13.85 microM. We believe that these two new scaffolds might be the good starting point from hit to lead optimization for new antitubercular agents.
Authors:
Muhammad Muddassar; Jae Wan Jang; Seung Kon Hong; Hong Seung Gon; Yong Seo Cho; Eunice Eunkyung Kim; Kyo Chang Keum; Taegwon Oh; Sang-Nae Cho; Ae Nim Pae
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-18
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  18     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2010-12-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  6914-21     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Center for Chemoinformatics Research, Life Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Antitubercular Agents / chemistry*,  pharmacology
Binding Sites
Combinatorial Chemistry Techniques
Computer Simulation
Databases, Factual
Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / chemistry,  metabolism
Mycobacterium tuberculosis / enzymology
Protein Structure, Tertiary
Chemical
Reg. No./Substance:
0/Antitubercular Agents; EC 1.3.1.9/Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)
Comments/Corrections
Erratum In:
Bioorg Med Chem. 2010 Nov 1;18(21):7700
Note: Gon, Hong Seung [correct to Hong, Seung Kon]
Bioorg Med Chem. 2010 Dec 1;18(23):8410

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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