Novel Indole based thiazolotriazole as diabetic inhibitors: Synthesis, biological evaluation, in-silico molecular docking and simulation study

In the current study, indole-based thiazolotriazole analogs (1–22) were screened for their antidiabetic activity and evaluated for their inhibition against α-amylase and α-glucosidase enzymes. Some analogs showed better inhibition than the standard. The analog 5 has an IC₅₀ value of 2.50 µM and 3.6 µM, 6 IC₅₀ value 7.65 µM, 8.60 µM, 7 IC₅₀ value 5.05 µM, 5.95 µM, 8 IC₅₀ value 1.65 µM, 2.10 µM, 12 IC₅₀ value 4.90 µM, 4.90 µM, 18 IC₅₀ value 5.30 µM, and 22 IC₅₀ value 1.65 µM, 2.40 µM for α-amylase and α-glucosidase enzymes, respectively, showing good inhibition against both enzymes. When compared with the standard drug Acarbose, having an IC₅₀ value of 9.15 ± 0.10 and 10.25 ± 0.10 µM for α-amylase and α-glucosidase enzymes, respectively. On the basis of the skeleton and different substituents on the aryl ring, the SAR has been established for all synthesized analogs. To study the mechanism of action, kinetic studies were performed. Molecular docking studies were carried out for potent analogs, which confirmed the binding interactions between ligands and the active site of the enzyme. The structures of all compounds were confirmed using NMR and HR-EIMS analyses.