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Synthesis, Molecular Dynamic, and in Silico Study of New Ethyl 4-Arylpyrimido[1,2-B]Indazole-2-Carboxylate: Potential Inhibitors of Α-Glucosidase Publisher



Gashghaee M1 ; Azizian H2 ; Adib M1 ; Mohammadikhanaposhtani M3 ; Mojtabavi S4 ; Faramarzi MA4 ; Rezaei Y5 ; Biglar M6 ; Larijani B6 ; Rastegar H7 ; Mahdavi M6
Authors

Source: Journal of Molecular Structure Published:2022


Abstract

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. © 2022
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