Design, synthesis, and enzyme kinetics of novel benzimidazole and quinoxaline derivatives as methionine synthase inhibitors.

摘要: Abstract Methionine synthase catalyzes the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine, producing methionine and tetrahydrofolate. Benzimidazole deazatetrahydrofolates derivatives have been shown inhibit by competing with substrate 5-methyltetrahydrofolate. In this study, novel series substituted benzimidazoles quinoxalines were designed assessed for inhibitory activity against purified rat liver using radiometric enzyme assay. Compounds 3g , 3j 5c showed highest (IC 50 : 20 μM, 18 μM, 9 μM, respectively). Kinetic analysis these compounds Lineweaver–Burk plots revealed characteristics mixed inhibition ; uncompetitive . Docking study into homology model gave insights molecular determinants class compounds. The identification drug-like inhibitors could lead design next generation modulators synthase.