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 ( 1 - 17 ) 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 ( 1 - 17 ) were characterized using a combination of several spectroscopic techniques, including FT-IR, 1 H-NMR, 13 C-NMR, and EI-MS. The majority of the synthesized compounds demonstrated a notable potency against α -glucosidase and urease enzymes. These analogues disclosed varying degrees of α -glucosidase and urease inhibitory activities, with their IC 50 values ranging from 2.50 to 17.50 μM ( α -glucosidase) and 14.30 to 41.50 (urease). Compounds 6 , 7 , 14 , and 12 , with IC 50 values of 2.50, 3.20, 3.40, and 3.50 μM as compared to standard acarbose (IC 50 = 5.30 µM), while the same compounds showed 14.30, 19.20, 21.80, and 22.30 comparable with thiourea (IC 50 = 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 6 was a dual potent inhibitor against α -glucosidase and urease due to the presence of -CF 3 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 50 values. Moreover, in silico studies on most active compounds, i.e., 6 , 7 , 14 , and 12 , were also performed to understand the binding interaction of most active compounds with active sites of α-glucosidase and urease enzymes.