Novel 3,5‐Dimethylpyrazole‐Linked 1,2,4‐Triazole‐3‐thiols as Potent Antihyperglycemic Agents: Synthesis, Biological Evaluation, and In Silico Molecular Modelling Investigations

Abstract In this work, a series of pyrazole‐linked 1,2,4‐triazole‐3‐thiol derivatives ( 3a–i ) were prepared and identified by 13 C NMR, 1 H NMR, and mass spectrometry (ESI‐MS) data. The newly synthesized molecules were also evaluated in vitro for their α‐amylase and α‐glucosidase inhibitory potential. All newly synthesized compounds exhibited potent α‐glucosidase inhibition activity with IC50 in the range of 1.016 ± 0.70 to 24.40 ± 0.02 µM and good α‐amylase inhibitory with IC50 in the range of 49.91 ± 0.32 to 500 µM, as compared to acarbose. The most potent compound among this series is derivative 3e , with IC50 value of 1.016 ± 0.70 µM, which is many folds more than that of acarbose. In addition, in docking studies, both compounds exhibited good interactions at the active region of target proteins. Therefore, this study may lead via structural modifications to the discovery of new potent α‐amylase and α‐glucosidase inhibitors useful in the diabetes treatment.