An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity.

In an attempt to find novel α-glucosidase inhibitors, an efficient, straightforward reaction to synthesize a library of fully substituted 6-amino-pyrazolo[1,5-a]pyrimidines 3 has been investigated. Heating a mixture of α-azidochalcones 1 and 3-aminopyrazoles 2 under the mild condition afforded desired compounds with a large substrate scope in good to excellent yields. All obtained products were evaluated as α-glucosidase inhibitors and exhibited excellent potency with IC50 values ranging from 15.2 ± 0.4 µM to 201.3 ± 4.2 µM. Among them, compound 3d was around 50-fold more potent than acarbose (IC50 = 750.0 ± 1.5 µM) as standard inhibitor. Regarding product structures, kinetic study and molecular docking were carried out for two of the most potent ones.

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

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.

Design and synthesis of new fused carbazole-imidazole derivatives as anti-diabetic agents: In vitro α-glucosidase inhibition, kinetic, and in silico studies.

Twenty three fused carbazole-imidazoles 6a-w were designed, synthesized, and screened as new α-glucosidase inhibitors. All the synthesized fused carbazole-imidazoles 6a-w were found to be more active than acarbose (IC50 = 750.0 ±â€¯1.5 µM) against yeast α-glucosidase with IC50 values in the range of 74.0 ±â€¯0.7-298.3 ±â€¯0.9 µM. Kinetic study of the most potent compound 6v demonstrated that this compound is a competitive inhibitor for α-glucosidase (Ki value = 75 µM). Furthermore, the in silico studies of the most potent compounds 6v and 6o confirmed that these compounds interacted with the key residues in the active site of α-glucosidase.