Development of hydroxybenzaldehyde-based pyrimidine-2-one scaffolds: synthesis, characterization, and α-glucosidase inhibitory activity

A series of new arylhydrazone derivatives of dihydropyrimidin-2-one (6a-6o) were prepared and assessed for their in vitro α-glucosidase inhibitory activity. The synthesis involved a three-step reaction process, beginning with the synthesis of the dihydropyrimidin-2-one scaffold, followed by the synthesis of a hydrazide derivative, and concluding with the synthesis of the target acylhydrazones. The in vitro assays revealed that several compounds exhibited significant α-glucosidase inhibition, with IC 50 values ranging from 53.43 ± 0.014 μM to 365.17 ± 0.01 μM, compared to the standard inhibitor Acarbose (IC 50 = 873.34 ± 1.67 μM). Molecular docking studies also validated further the binding interactions of the best and worst inhibitors within the active site of α-glucosidase, emphasizing important hydrophobic and hydrogen-bonding interactions. Such findings indicate that the synthesized compounds, especially 6 k (IC 50 = 53.43 ± 0.014 μM), promise to be therapeutic potential to treat postprandial hyperglycemia in type-II diabetes.