Unveiling the Novel Triazole Hybrids as Dual Antidiabetic Activities: In Vitro and In Silico Studies

We have investigated synthesis, spectral analysis, and DFT calculations of β‐amino‐crotonate‐based novel 1,2,4‐triazole derivatives (3A‐3I) with antidiabetic activities. Research published between 2018 and 2025 shows that triazole coupled with heterocyclic ring structures has promising dual enzyme inhibition moderate for antidiabetic effects. The compound 3B containing fluorine group at para position of aryl ring demonstrated moderate α‐amylase activity, similarly, with an IC 50 value of 65.74 µg/mL. The compound 3A containing chlorine at the ortho position of aryl ring exhibited the moderate α‐amylase inhibitory activity. The compounds 3B and 3A exhibited good in vitro α‐glucosidase inhibitory activities with an IC 50 value of 76.48 and 77.31 µg/mL, respectively, as compare to other compounds and acarbose. In silico studies revealed that compound 3B interacts with three enzyme active site hydrogen bonds. In vivo results showed that the analysis of glucose levels in the hemolymph homogenate revealed that the fly group treated with acarbose exhibited a considerable reduction in glucose levels compared to the control group. These findings were showed that triazole‐derived crotonate moiety function as α‐amylase α‐glucosidase enzyme inhibitors, which aid in the development of new treatments for diabetes mellitus and can serve as lead molecules in drug discovery as possible antidiabetic medicines.