Design and synthesis of novel imidazolidine-2,4-dione derivatives as InhA inhibitors: Spectral characterization, computational, and biological studies

Abstract

Tuberculosis is a global disease caused by bacteria called Mycobacterium tuberculosis (M.tb) and is one of the top 10 causes of death from a single infectious agent. InhA (enoyl acylcarrier proteinreductase) from M.tb is the target that is involved in cell wall biosynthesis. The most effective drug to treat TB (tuberculosis) is INH (isoniazide) which is a prodrug, activated by KatG (catalase-peroxidaseenzyme) to generate isonicotinoyl radical that reacts with NAD (nicotinamide adenine dinucleotide) to form an INH-NADH complex, acting as a real InhA inhibitor. A series of novel imidazolidine-2,4-dione were designed by site identification and molecular docking using GLIDE. After synthesis, the compounds were characterized by 1H NMR, LC-MS, FT-IR, and elemental analysis. The compounds were found to be moderately active against M.tb. MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) assay was used to test the compounds for anticancer activity against human breast cancer cell line MCF-7.