Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents

In the present study, new structural variants of 4-hydroxyquinolinone-hydrazones were designed and synthesized. The structure elucidation of the synthetic derivatives 6a-o was carried out using different spectroscopic techniques including FTIR, H-1-NMR, C-13-NMR, and elemental analysis, and their alpha-glucosidase inhibitory activity was also determined. The synthetic molecules 6a-o exhibited good alpha-glucosidase inhibition with IC50 values ranging between 93.5 +/- 0.6 to 575.6 +/- 0.4 mu M as compared to the standard acarbose (IC50 = 752.0 +/- 2.0 mu M). Structure-activity relationships of this series were established which is mainly based on the position and nature of the substituent on the benzylidene ring. A kinetic study of the active compounds 6l and 6m as the most potent derivatives were also carried out to confirm the mode of inhibition. The binding interactions of the most active compounds within the active site of the enzyme were determined by molecular docking and molecular dynamic simulations.

Automated summary

In this study, new structural variants of 4-hydroxyquinolinone-hydrazones were designed and synthesized. The structure elucidation of the synthetic derivatives 6a-o was determined using various spectroscopic techniques, and their alpha-glucosidase inhibitory activity was evaluated. The synthetic molecules exhibited good alpha-glucosidase inhibition with IC50 values ranging from 93.5 +/- 0.6 to 575.6 +/- 0.4 μM, compared to the standard acarbose (IC50 = 752.0 +/- 2.0 μM). Structure-activity relationships and the mode of inhibition were established through kinetic studies and molecular docking simulations.