Pyrazole-Imidazopyridine Hydrazones: Synthesis, -Glucosidase, -Amylase Inhibitory Activity and Computational Studies

Diabetic complications poses major threat to mankind which found to be dangerously fatal all over the world. It is thought vital to find new class of molecules to combat diabetic problems. Thus, in continuation of our efforts in identifying new class of a-glucosidase and a-amylase inhibitors, a novel series of hybrid molecules comprising of imidazo[1,2-alpha]pyridine and pyrazoles, i. e. (3-(Substituted phenyl)-1H-pyrazol-4-yl)methylene)-2,7-dimethyl-1H-imidazo[1,2-alpha]pyridine-3-carbohydrazide derivatives (8a-m) were designed through a acyl hydrazone bridge. The compound (Z)-N'-({3-[4-(2-Fluorobenzyloxy)phenyl]1H-pyrazol-4-yl}methylene)-2,7-dimethyl-imidazo[1,2-alpha]pyridine-3-carbohydrazide (8m) emerged as potent inhibitor of aglucosidase and alpha-amylase enzyme with IC50 5.00 +/- 0.10 mu g/mL and 15 +/- 0.35 mu g/mL respectively. The enzyme kinetics studies revealed reversible non-competitive mode of inhibition of 8m against both enzymes. In addition, these compounds were subjected to detailed in-silico studies to understand their interaction with respective target proteins.