Synthesis of diethyl 4-substituted-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates as a new series of inhibitors against yeast α-glucosidase

Abstract

1,4-Dihydropyridine-3,5-dicarboxylate derivatives (1–25) were synthesized in high yields via Hantzsch reaction and evaluated for their α-glucosidase inhibitory activity. Compounds 1, 2, 6–8, 11, 13–15, and 23–25 showed a potent inhibitory activity against yeast α-glucosidase with IC50 values in the range of 35.0–273.7 μM, when compared with the standard drug acarbose (IC50 = 937 ± 1.60 μM). Their structures were characterized by different spectroscopic techniques. The kinetics, selectivity, and toxicity studies on these compounds were also carried out. The kinetic studies on most active compounds 14 and 25 determined their modes of inhibition and dissociation constants Ki. Compound 14 was found to be a non-competitive inhibitor with Ki = 25.0 ± 0.06, while compound 25 was identified as a competitive inhibitor with Ki = 66.0 ± 0.07 μM.