Dihydropyrano [2,3-c] pyrazole: Novel in vitro inhibitors of yeast α-glucosidase

Abstract

Inhibition of α-glucosidase enzyme activity is a reliable approach towards controlling post-prandial hyperglycemia associated risk factors. During the current study, a series of dihydropyrano[2,3-C] pyrazoles (1-35) were synthesized and evaluated for their α-glucosidase inhibitory activity. Compounds 1,4,22,30, and 33 were found to be the potent inhibitors of the yeast α-glucosidase enzyme. Mechanistic studies on most potent compounds reveled that 1,4, and 30 were non-competitive inhibitors (Ki=9.75 ± 0.07, 46 ± 0.0001, and 69.16 ± 0.01 μM, respectively), compound 22 is a competitive inhibitor (Ki=190 ± 0.016 μM), while 33 was an uncompetitive inhibitor (Ki=45 ± 0.0014 μM) of the enzyme. Finally, the cytotoxicity of potent compounds (i.e. Compounds 1, 4, 22, 30, and 33) was also evaluated against mouse fibroblast 3T3 cell line assay, and no toxicity was observed.