Identification of novel antitubercular compounds through hybrid virtual screening approach

Muhammad Muddassar, Jae Wan Jang, Hong Seung Gon, Yong Seo Cho, Eunice Eunkyung Kim, Kyo Chang Keum, Taegwon Oh, Sang Nae Cho, Ae Nim Pae

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


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 μM and another showed MIC of 13.85 μM. We believe that these two new scaffolds might be the good starting point from hit to lead optimization for new antitubercular agents.

Original languageEnglish
Pages (from-to)6914-6921
Number of pages8
JournalBioorganic and Medicinal Chemistry
Issue number18
Publication statusPublished - 2010 Sept 15

Bibliographical note

Funding Information:
This work was supported by Korea Functional Proteomic Center, 21C Frontier Program of Korea Ministry of Education, Science and Technology and Grants from Korea Institute of Science and Technology (2E21590).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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