Elucidation of binding mechanism of rhodanine derivative P4OC on bovine serum albumin

• Published in: Journal of biomolecular structure & dynamics 2024-01, Vol.42 (1), p.475-482
• Main Authors: Sampath, Sakthiprabha, Yadav, Sangilimuthu Alagar, Meti, Manjunath, Kaveri, Sundaram, Subban, Ravi, Subramanyam, Rajagopal
• Format: Article
• Language: English
• Subjects: binding properties; Binding Sites; bovine serum albumin; Circular Dichroism; fluorescence quenching; Molecular Docking Simulation; P4OC; Protein Binding; Rhodanine - pharmacology; Rhodanine derivatives; Serum Albumin, Bovine - chemistry; Spectrometry, Fluorescence - methods; Spectrophotometry, Ultraviolet; Thermodynamics
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2023.2194001

Rhodanine is an important scaffold in medicinal chemistry and it act as potent anticancer agent and other pharmacological effects. In pharmacokinetics and pharmacodynamics studies of the drug, the drug binding properties on serum protein is crucial for producing better drug. This study was designed to explore the binding interactions between the Rhodanine derivative (P4OC) on Bovine Serum Albumin (BSA). The interactions between P4OC and BSA were investigated using biophysical approach and molecular docking. The quenching mechanism and binding constants of P4OC on BSA were determined by biophysical approach through fluorescence spectroscopic experiments. Circular dichroism (CD) spectroscopy was used to study the secondary structural changes of BSA upon P4OC binding. The fluorescence experiments of P4OC binding on BSA show good drug binding with static quenching constants using stern Volmer plot and found the quenching constant value K P4OC = 1.12762 × 10 13 M −1 with corresponding binding free energy (ΔG) −2.303 kcal/mol. The molecular displacement fluorescence emission on BSA-P4OC complex by site specific markers shows that P4OC binds at I A sub-domain of BSA further confirmed peak shift by synchronous fluorescence of P4OC on BSA with tyrosine, tryptophan and phenylalanine amino acids. Increasing concentration of P4OC on BSA found secondary structural changes, the percentage of α-helix was decreased as well increase percentage of β-sheet and random coil. The binding of P4OC to BSA was computationally studied by molecular docking methods. Thus, results obtained are in excellent agreement with experimental and theoretical results with respect to the binding mechanism and binding constant of P4OC on BSA. We concluded that, the rhodanine derivative P4OC possesses good drug binding properties on BSA. Further P4OC may be evaluated its potential pharmacological activities on clinical trial. Communicated by Ramaswamy H. Sarma