Synthesis and Evaluation of 1,3,5-Triaryl-2-Pyrazoline Derivatives as Potent Dual Inhibitors of Urease and α-Glucosidase Together with Their Cytotoxic, Molecular Modeling and Drug-Likeness Studies.

In the present work, a concise library of 1,3,5-triaryl-2-pyrazolines () was designed and synthesized by employing a multistep strategy, and the newly synthesized compounds were screened for their urease and α-glucosidase inhibitory activities. The compounds () were characterized using a combination of several spectroscopic techniques including FT-IR, H NMR, C NMR, and EI-MS. All the synthesized compounds, except compound were potent against urease as compared to the standard inhibitor thiourea (IC = 21.37 ± 0.26 μM). These analogs disclosed varying degrees of urease inhibitory activities ranging from 9.13 ± 0.25 to 18.42 ± 0.42 μM. Compounds , and having IC values of 9.36 ± 0.27, 9.13 ± 0.25, 9.18 ± 0.35, and 9.35 ± 0.35 μM, respectively, showed excellent inhibitory activity as compared to standard thiourea (IC = 21.37 ± 0.26 μM). A kinetic study of compound revealed that compound inhibited urease in a competitive mode. Among the synthesized pyrazolines, the compounds , and exhibited excellent α-glucosidase inhibitory activity with the lowest IC values of 212.52 ± 1.31, 237.26 ± 1.28, 138.35 ± 1.32, and 114.57 ± 1.35 μM, respectively, as compared to the standard acarbose (IC = 375.82 ± 1.76 μM). The compounds ( showed α-glucosidase IC values in the range of 114.57 ± 1.35 to 462.94 ± 1.23 μM. Structure-activity relationship revealed that the size and electron-donating or -withdrawing effects of substituents influenced the activities, which led to the urease and α-glucosidase inhibiting properties. Compound was a dual potent inhibitor against urease and α-glucosidase due to the presence of 2-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 urease and α-glucosidase with minimum IC values. The cytotoxicity of the compounds () was also investigated against human cell lines MCF-7 and HeLa. Compound showed moderate cytotoxic activity against MCF-7 and HeLa cell lines. Moreover, in silico studies on most active compounds were also performed to understand the binding interaction of most active compounds with active sites of urease and α-glucosidase enzymes. Some compounds exhibited drug-like characteristics due to their lower cytotoxic and good ADME profiles.