The Synthesis, In Vitro Bio-Evaluation, and In Silico Molecular Docking Studies of Pyrazoline-Thiazole Hybrid Analogues as Promising Anti-α-Glucosidase and Anti-Urease Agents.

In the present work, a concise library of benzothiazole-derived pyrazoline-based thiazole (-) was designed and synthesized by employing a multistep reaction strategy. The newly synthesized compounds were screened for their α-glucosidase and urease inhibitory activities. The scaffolds (-) were characterized using a combination of several spectroscopic techniques, including FT-IR, H-NMR, C-NMR, and EI-MS. The majority of the synthesized compounds demonstrated a notable potency against -glucosidase and urease enzymes. These analogues disclosed varying degrees of -glucosidase and urease inhibitory activities, with their IC values ranging from 2.50 to 17.50 μM (-glucosidase) and 14.30 to 41.50 (urease). Compounds , , , and , with IC values of 2.50, 3.20, 3.40, and 3.50 μM as compared to standard acarbose (IC = 5.30 µM), while the same compounds showed 14.30, 19.20, 21.80, and 22.30 comparable with thiourea (IC = 31.40 μM), respectively, showed excellent inhibitory activity. The structure-activity relationship revealed that the size and electron-donating or electron-withdrawing effects of substituents influenced the enzymatic activities such as α-glucosidase and urease. Compound was a dual potent inhibitor against -glucosidase and urease due to the presence of -CF electron-withdrawing functionality on the phenyl ring. To the best of our knowledge, these synthetic compounds were found to be the most potent dual inhibitors of α-glucosidase and urease with minimum IC values. Moreover, in silico studies on most active compounds, i.e., , , , and , were also performed to understand the binding interaction of most active compounds with active sites of α-glucosidase and urease enzymes.