Muddassar, Muhammad Jang, Jae Wan Hong, Seung Gon Cho, Yong Seo Kim, Eunice Eunkyung Keum, Kyo Chang Oh, Taegwon Cho, Sang-Nae Pae, Ae Nim 2024-01-20T18:33:18Z 2024-01-20T18:33:18Z 2021-09-05 2010-09-15 0968-0896 https://pubs.kist.re.kr/handle/201004/131103 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 mu M and another showed MIC of 13.85 mu M. We believe that these two new scaffolds might be the good starting point from hit to lead optimization for new antitubercular agents. (C) 2010 Elsevier Ltd. All rights reserved. English PERGAMON-ELSEVIER SCIENCE LTD CARRIER PROTEIN REDUCTASE MYCOBACTERIUM-TUBERCULOSIS LIGAND DOCKING INHA INHIBITORS TRICLOSAN RESISTANT TARGET Identification of novel antitubercular compounds through hybrid virtual screening approach Article 10.1016/j.bmc.2010.07.010 1 BIOORGANIC & MEDICINAL CHEMISTRY, v.18, no.18, pp.6914 - 6921 BIOORGANIC & MEDICINAL CHEMISTRY 18 18 6914 6921 scie scopus 000281524700033 2-s2.0-77956317548 Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic Biochemistry & Molecular Biology Pharmacology & Pharmacy Chemistry Article CARRIER PROTEIN REDUCTASE MYCOBACTERIUM-TUBERCULOSIS LIGAND DOCKING INHA INHIBITORS TRICLOSAN RESISTANT TARGET Mycobacterium tuberculosis Antimicrobial agents Ligand based Structure based Virtual screening