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

Abstract

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.

Interaction of 4′-methylflavonoids with biological membranes, liposomes, and human albumin

“…These results are in line with another data 43 , 47 and our previously published studies 48 . Moreover, in silico and in vitro studies validated the moderate binding of chalcone with BSA 49 , 50 . Molecular docking and molecular dynamic simulation studies suggested the stabile binding of chalcone with the BSA microenvironment 49 .…”

“…Moreover, in silico and in vitro studies validated the moderate binding of chalcone with BSA 49 , 50 . Molecular docking and molecular dynamic simulation studies suggested the stabile binding of chalcone with the BSA microenvironment 49 . Major structural differences between the compounds used in our study are related to the ring C which correlates with binding to HSA.…”

Design and synthesis of ferrocene‐tethered pyrazolines and pyrazoles: Photophysical studies, protein‐binding behavior with bovine serum albumin, and antiproliferative activity against MDA‐MB‐231 triple negative breast cancer cells

“…Besides, it is a popular approach to substitute HSA with BSA to represent the serum albumins in protein ligand interaction studies. [ 35 ] We investigated the biophysical interactions of the chosen compound 4g with BSA through steady‐state absorption spectra. The absorption spectra of BSA show characteristic bands, at around 280 nm.…”

One‐step preparation of red‐emitting carbon dots for visual and quantitative detection of copper ions

“…[ 61,62 ] The UV–vis absorption of R‐CDs and R‐CDs‐Cu 2+ (40 μM) system in Figure 5 (a) did not coincide, indicating that the mechanism of Cu 2+ quenching R‐CDs was the static quenching mechanism or the combination mechanism of static and dynamic quenching. [ 63 ] In addition, the dynamic quenching mechanism, the static quenching mechanism and the combination mechanism of static and dynamic quenching can be distinguished by measuring the fluorescence lifetime of the fluorescent probe before and after quenching. If the fluorescence lifetimes before and after quenching are the same, the quenching mechanism is static quenching mechanism, if the fluorescence lifetimes before and after quenching are different, the quenching mechanism is the dynamic quenching mechanism or the combination of static and dynamic quenching.…”