Inhibition of M. tuberculosis β-ketoacyl CoA reductase FabG4 (Rv0242c) by triazole linked polyphenol-aminobenzene hybrids: comparison with the corresponding gallate counterparts

Deb Ranjan Banerjee; Kalyan Senapati; Rupam Biswas; Amit K Das; Amit Basak

doi:10.1016/j.bmcl.2015.01.014

Inhibition of M. tuberculosis β-ketoacyl CoA reductase FabG4 (Rv0242c) by triazole linked polyphenol-aminobenzene hybrids: comparison with the corresponding gallate counterparts

Bioorg Med Chem Lett. 2015 Mar 15;25(6):1343-7. doi: 10.1016/j.bmcl.2015.01.014. Epub 2015 Jan 22.

Authors

Deb Ranjan Banerjee¹, Kalyan Senapati¹, Rupam Biswas², Amit K Das³, Amit Basak⁴

Affiliations

¹ Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India.
² Department of Biotechnology, Indian Institute of Technology, Kharagpur 721302, India.
³ Department of Biotechnology, Indian Institute of Technology, Kharagpur 721302, India. Electronic address: [email protected].
⁴ Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India. Electronic address: [email protected].

PMID: 25666821
DOI: 10.1016/j.bmcl.2015.01.014

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.

Keywords: FabG4; Fatty acid synthesis; Inhibition; Micromolar; SAR; Tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alcohol Oxidoreductases / antagonists & inhibitors*
Alcohol Oxidoreductases / metabolism
Antitubercular Agents / chemical synthesis
Antitubercular Agents / chemistry*
Antitubercular Agents / pharmacology
Binding Sites
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Molecular Docking Simulation
Mycobacterium tuberculosis / drug effects
Mycobacterium tuberculosis / enzymology*
Polyphenols / chemistry
Protein Binding
Protein Structure, Tertiary
Structure-Activity Relationship
Triazoles / chemical synthesis
Triazoles / chemistry*
Triazoles / pharmacology

Substances

Antitubercular Agents
Enzyme Inhibitors
Polyphenols
Triazoles
Alcohol Oxidoreductases
acetoacetyl-CoA reductase