Novel acyl hydrazide derivatives of polyhydroquinoline as potent anti-diabetic and anti-glycating agents: Synthesis, in vitro α-amylase, α-glucosidase inhibition and anti-glycating activity with molecular docking insights

In this study, eleven novel acyl hydrazides derivative of polyhydroquinoline were synthesized, characterized and screened for their in vitro anti-diabetic and anti-glycating activities. Seven compounds 2a, 2d, 2i, 2 h, 2j, 2f, and 2 g exhibited notable alpha-amylase inhibitory activity having IC50 values from 3.51 +/- 2.13 to 11.92 +/- 2.30 mu M. Similarly, six compounds 2d, 2f, 2 h, 2i, 2j, and 2 g displayed potent alpha-glucosidase inhibitory activity compared to the standard acarbose. Moreover, eight derivatives 2d, 2 g, 2f, 2j, 2a, 2i, 2 g, and 2e showed excellent antiglycating activity with IC50 values from 6.91 +/- 2.66 to 15.80 +/- 1.87 mu M when compared them with the standard rutin (IC50 = 22.5 +/- 0.90 mu M). Molecular docking was carried out to predict the binding modes of all the compounds with alpha-amylase and alpha-glucosidase. The docking analysis revealed that most of the compounds established strong interactions with alpha-amylase and alpha-glucosidase. All compounds fitted well into the binding pockets of alpha-amylase and alpha-glucosidase. Among all compounds 2a and 2f were most potent based on docking score -8.2515 and -7.3949 against alpha-amylase and alpha-glucosidase respectively. These results hold promise for the development of novel candidates targeted at controlling postprandial glucose levels in individuals with diabetes.