Privileged Scaffold Chalcone: Synthesis, Characterization and Its Mechanistic Interaction Studies with BSA Employing Spectroscopic and Chemoinformatics Approaches

[Image: see text] Chalcone, a privileged structure, is considered as an effective template in the field of medicinal chemistry for potent drug discovery. In the present study, a privileged template chalcone was designed, synthesized, and characterized by various spectroscopic techniques (NMR, high-resolution mass spectrometry, Fourier transform infrared (FT-IR) spectroscopy, UV spectroscopy, and single-crystal X-ray diffraction). The mechanism of binding of chalcone with bovine serum albumin (BSA) was determined by multispectroscopic techniques and computational methods. Steady-state fluorescence spectroscopy suggests that the intrinsic fluorescence of BSA was quenched upon the addition of chalcone by the combined dynamic and static quenching mechanism. Time-resolved spectroscopy confirms complex formation. FT-IR and circular dichroism spectroscopy suggested the presence of chalcone in the BSA molecule microenvironment and also the possibility of rearrangement of the native structure of BSA. Moreover, molecular docking studies confirm the moderate binding of chalcone with BSA and the molecular dynamics simulation analysis shows the stability of the BSA–drug complex system with minimal deformability fluctuations and potential interaction by the covariance matrix. Moreover, pharmacodynamics and pharmacological analysis show good results through Lipinski rules, with no toxicity profile and high gastrointestinal absorptions by boiled egg permeation assays. This study elucidates the mechanistic profile of the privileged chalcone scaffold to be used in therapeutic applications.