TitleAnti-tubercular activity and molecular docking studies of indolizine derivatives targeting mycobacterial InhA enzyme.
Publication TypeJournal Article
Year of Publication2021
AuthorsVenugopala KN, Chandrashekharappa S, Deb PKishore, Tratrat C, Pillay M, Chopra D, Al-Shar'i NA, Hourani W, Dahabiyeh LA, Borah P, Nagdeve RD, Nayak SK, Padmashali B, Morsy MA, Aldhubiab BE, Attimarad M, Nair AB, Sreeharsha N, Haroun M, Shashikanth S, Mohanlall V, Mailavaram R
JournalJ Enzyme Inhib Med Chem
Date Published2021 Dec
KeywordsAntitubercular Agents, Bacterial Proteins, Indolizines, Microbial Sensitivity Tests, Molecular Docking Simulation, Mycobacterium tuberculosis, Oxidoreductases

A series of 1,2,3-trisubstituted indolizines (, and ) were screened for whole-cell anti-tubercular activity against the susceptible H37Rv and multidrug-resistant (MDR) (MTB) strains. Compounds , , and were active against the H37Rv-MTB strain with minimum inhibitory concentration (MIC) ranging from 4 to 32 µg/mL, whereas the indolizines with ethyl ester group at the 4-position of the benzoyl ring also exhibited anti-MDR-MTB activity (MIC = 16-64 µg/mL). docking study revealed the enoyl-acyl carrier protein reductase (InhA) and anthranilate phosphoribosyltransferase as potential molecular targets for the indolizines. The X-ray diffraction analysis of the compound was also carried out. Further, a safety study ( and ) demonstrated no toxicity for these compounds. Thus, the indolizines warrant further development and may represent a novel promising class of InhA inhibitors and multi-targeting agents to combat drug-sensitive and drug-resistant MTB strains.

Alternate JournalJ Enzyme Inhib Med Chem
PubMed ID34210233
PubMed Central IDPMC8259857