Experimental and Computational Validation of Structural Features and BSA Binding Tendency of 5‐Hydroxy‐5‐trifluoromethyl‐3‐arylpyrazolines**

Abstract

AbstractBovine serum albumin (BSA) serves as a model protein to explore drug‐protein interactions due to its structural similarities with Human serum albumin (HSA). In this report, the binding tendency of BSA protein with synthesized trifluoromethyl functionalized pyrazoles i. e., 5‐hydroxy‐3‐(p‐methoxyphenyl)‐5‐trifluoromethyl‐4,5‐dihydropyrazole‐1‐thiocarboxamide (2 a) and 5‐hydroxy‐3‐(p‐bromophenyl)‐5‐trifluoromethyl‐4,5‐dihydropyrazole‐1‐thiocarboxamide (2 b) was explored using spectroscopic techniques. The pyrazoles were synthesized by a one‐pot reaction and characterized with the help of single‐crystal X‐ray diffraction. The crystallographic parameters were found to be in close agreement with those evaluated computationally using density functional theory (DFT). Further, to explore the nature of interactions involved in binding, Hirshfeld surface analysis was carried out, which indicated the presence of non‐covalent interactions. Specifically, hydrogen bonding viz O−H, S−H and F−H were observed in both cases. As predicted by DFT based global reactivity descriptors, compound 2 a is chemically softer than 2 b. In silico molecular docking and molecular dynamic studies were also performed to validate the nature of binding interactions present in both cases.