Anti-tubercular activity and molecular docking studies of indolizine derivatives targeting mycobacterial InhA enzyme.
Title | Anti-tubercular activity and molecular docking studies of indolizine derivatives targeting mycobacterial InhA enzyme. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Venugopala 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 |
Journal | J Enzyme Inhib Med Chem |
Volume | 36 |
Issue | 1 |
Pagination | 1472-1487 |
Date Published | 2021 Dec |
ISSN | 1475-6374 |
Keywords | Antitubercular Agents, Bacterial Proteins, Indolizines, Microbial Sensitivity Tests, Molecular Docking Simulation, Mycobacterium tuberculosis, Oxidoreductases |
Abstract | 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. |
DOI | 10.1080/14756366.2021.1919889 |
Alternate Journal | J Enzyme Inhib Med Chem |
PubMed ID | 34210233 |
PubMed Central ID | PMC8259857 |