Multi-spectroscopic investigation, molecular docking and molecular dynamic simulation of competitive interactions between flavonoids (quercetin and rutin) and sorafenib for binding to human serum albumin

Abstract

The main mechanism for drug-drug interaction is displacement reaction of ligands from their protein binding sites. The aim of this study was to evaluate anticancer drug sorafenib displacement from the binding site on human serum albumin by commonly used plant flavonoids quercetin and rutin. The interaction between bio-macromolecules and drugs can also cause changes in protein structure and therefore was evaluated in this study by spectroscopic and molecular dynamic simulation techniques. Serum albumin, the main protein in the plasma acts in the disposition of many drugs and therefore, is a model protein for investigating drug/ligand binding and alteration in the spectrophotometric and molecular docking properties of drug/ligand. All the studied ligands sorafenib, quercetin and rutin bind to HSA with different binding affinity. The displacement of ligands from their binding sites was inferred from comparison of quenching and binding constants of binary and ternary systems. Conformational changes in the HSA were found with UV-spectroscopic, circular dichroism, FT-IR and three dimensional studies. The molecular dynamic simulation studies suggest a stable complex formation between HSA and sorafenib. Binding studies for HSA-sorafenib in presence of quercetin and rutin indicated displacement of sorafenib from its binding site.

Keywords: Binding interaction; Fluorescence quenching; Human serum albumin; Quercetin; Rutin; Sorafenib.