Design and synthesis of new imidazo [1, 2-b] pyrazole derivatives, in vitro α-glucosidase inhibition, kinetic and docking studies

Peytam F, Adib M, Shourgeshty R, Mohammadi-Khanaposhtani M, Jahani M, Imanparast S, Faramarzi MA, Mahdavi M, Moghadamnia AA, Rastegar H, Larijani B.

Molecular Diversity. 2020 Feb;24(1):69-80.

2020

A new series of imidazo[1,2-b]pyrazole derivatives 4a–o was designed, synthesized, and screened for in vitro α-glucosidase inhibitory activity. All compounds showed high inhibitory activity in the range of IC₅₀ = 95.0 ± 0.5–372.8 ± 1.0 µM as compared to standard drug acarbose (IC₅₀ = 750 ± 1.5 µM) and were also found to be non-cytotoxic. Among the synthesized compounds, the most potent compound was compound 4j with eightfold higher inhibitory activity compared to acarbose. Like acarbose, compound 4j inhibited α-glucosidase in a competitive mode. Molecular modeling studies of the most potent compounds 4j, 4f, 4o, and 4c were also conducted.