Synthesis, molecular dynamic, and in silico study of new ethyl 4-arylpyrimido[1,2-b]indazole-2-carboxylate: Potential inhibitors of α-glucosidase

A new series of ethyl 4-arylpyrimido[1,2-b]indazole-2-carboxylate derivatives 7a-p were synthesized and screened for their α-glucosidase inhibitory activity. The half of these new compounds displayed inhibitory activity against α-glucosidase, with IC50 values in the range of 66.98 ± 0.05–650.30 ± 0.08 µM as compared to acarbose as standard inhibitor with IC50 value of 762.59 ± 0.04 µM. Among the title compounds, compound 7n presented the most inhibition effect against α-glucosidase. Kinetic study revealed that compound 7n is a competitive inhibitor with a Ki value of 66 µM. In addition, by performing molecular dynamic investigation and MM-GBSA calculation, we investigated the difference in structural perturbation and dynamic behavior that is observed over α-glucosidase in complex with the most active compound and acarbose relative to unbound α-glucosidase enzyme