Development of benzo[d]oxazol-2(3H)-ones derivatives as novel inhibitors of Mycobacterium tuberculosis InhA
| Autor: | Shailendra K. Saxena, Janupally Renuka, Variam Ullas Jeankumar, Perumal Yogeeswari, Ganesh S. Pedgaonkar, Parthiban Brindha Devi, Jonnalagadda Padma Sridevi, Dharmarajan Sriram |
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| Rok vydání: | 2014 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Antitubercular Agents Pharmaceutical Science Microbial Sensitivity Tests Reductase Biochemistry Cell Line Mycobacterium tuberculosis chemistry.chemical_compound Mice Structure-Activity Relationship Bacterial Proteins Drug Discovery Animals Humans Tuberculosis Cytotoxicity Molecular Biology IC50 Benzoxazoles biology Chemistry INHA Organic Chemistry biology.organism_classification In vitro Molecular Docking Simulation Cell culture Molecular Medicine Oxidoreductases Acetamide |
| Zdroj: | Bioorganicmedicinal chemistry. 22(21) |
| ISSN: | 1464-3391 |
| Popis: | A series of twenty seven substituted 2-(2-oxobenzo[d]oxazol-3(2H)-yl)acetamide derivatives were designed based on our earlier reported Mycobacterium tuberculosis (MTB) enoyl-acyl carrier protein reductase (InhA) lead. Compounds were evaluated for MTB InhA inhibition study, in vitro activity against drug-sensitive and -resistant MTB strains, and cytotoxicity against RAW 264.7 cell line. Among the compounds tested, 2-(6-nitro-2-oxobenzo[d]oxazol-3(2H)-yl)-N-(5-nitrothiazol-2-yl)acetamide (30) was found to be the most promising compound with IC50 of 5.12 ± 0.44 μM against MTB InhA, inhibited drug sensitive MTB with MIC 17.11 μM and was non-cytotoxic at 100 μM. The interaction with protein and enhancement of protein stability in complex with compound 30 was further confirmed biophysically by differential scanning fluorimetry. |
| Databáze: | OpenAIRE |
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