Mechanistic Insight of Synthesized 1,4-Dihydropyridines as an Antidiabetic Sword against Reactive Oxygen Species.

The pharmacologically privileged DHP derivatives were synthesized using the pragmatic multicomponent Hantzsch synthesis to screen the antidiabetic activity. Initially, the candidates were screened using an blood glucose test, where compound showed the most prominent antidiabetic effect (% potency = 218%) compared to glimepiride. Then, a propositioned structure-activity relationship study was executed to reveal that longer side chains decreased the DHP's antidiabetic action. Mechanistically, compound diminished ROS in β-cells and muscle cells simultaneously, which was proved by enhanced serum biochemical markers. Also, compound decreased blood glucose by α-glucosidase inhibition (IC = 4.48 ± 0.32 μM), compared to acarbose (7.40 ± 0.41 μM), based selectively on the plasma window of . Acarbose demonstrated auspicious inhibitor activity according to the binding affinity (Δ), which was slightly lower than that of compound (-54.7 and -46.8 kcal/mol, respectively). During the 100 ns molecular dynamics simulations, the structural and energetic assessments exposed the high consistency of compound to bind to the α-glucosidase.