title: Inhibition of M. tuberculosis β-ketoacyl CoA reductase FabG4 (Rv0242c) by triazole linked polyphenol-aminobenzene hybrids: comparison with the corresponding gallate counterparts.
abstract: Herein we report six novel triazole linked polyphenol-aminobenzene hybrids (3-8) as inhibitors of Mycobacterium tuberculosis FabG4 (Rv0242c), a less explored β-ketoacyl CoA reductase that has immense potential to be the future anti-tuberculosis drug target due to its possible involvement in drug resistance and latent infection. Novel triazole linked polyphenol-aminobenzene hybrids have been synthesized, characterized and evaluated for their inhibitory activity against FabG4. All of them inhibit FabG4 at low micromolar concentrations. In silico docking study has been carried out to explain the experimental findings. A comparative study of these new inhibitors with previously reported gallate counterparts leads to structure-activity relations (SAR) of substituent linked to N-1 of triazole ring.
authors: Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India.
authors: Deb Ranjan
authors: DR
authors: Banerjee
authors: Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India.
authors: Kalyan
authors: K
authors: Senapati
authors: Department of Biotechnology, Indian Institute of Technology, Kharagpur 721302, India.
authors: Rupam
authors: R
authors: Biswas
authors: Department of Biotechnology, Indian Institute of Technology, Kharagpur 721302, India. Electronic address: amitk@hijli.iitkgp.ernet.in.
authors: Amit K
authors: AK
authors: Das
authors: Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India. Electronic address: absk@chem.iitkgp.ernet.in.
authors: Amit
authors: A
authors: Basak
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology*; D059808:Polyphenols / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D059808:Polyphenols; D014230:Triazoles; D000429:Alcohol Oxidoreductases; C023744:acetoacetyl-CoA reductase
keywords: FabG4; Fatty acid synthesis; Inhibition; Micromolar; SAR; Tuberculosis