Investigation molecular mechanism studies of the rosuvastatin interaction with human serum albumin using spectroscopic and molecular docking methods

Abstract

Introduction: Rosuvastatin is an HMG-CoA Reductase inhibitor which is one of the most widely used anti-cholesterol drugs. HSA, as the carrier of most drugs, plays an important role in drugs pharmacokinetics and pharmacodynamics. Investigation of Drug - HSA interaction could provide useful information for the researchers. Objective: the aim of this study is to investigate the molecular mechanism of interaction between rosuvastatin and HSA using multi-spectroscopic ,SPR and molecular modeling methods. Materials and Methods: The emission spectrum of HSA solution was recorded before and after adding different concentrations of rosuvastatin. The effect of internal filter and conformational changes was investigated using UV-Vis spectroscopy. Using SPR studies, the association and the dissociation rate constants were calculated. Site markers competitive study and molecular modeling were used to the location and mod of binding. The Stern-Volmer, Hill, Vant Hoff and Gibs equations to obtain binding constants and thermodynamic constants. SPR data were fitted to the 1: 1 interaction model to obtain rate constants. Results: Spectroscopic studies showed that rosuvastatin interacts with HSA via a static mechanism, while van der Waals and hydrogen forces are involved in the complex formation with sites IIA and IIIA. The results of FT-IR showed a change in the secondary structure of HSA in the presence of rosuvastatin. SPR studies, showed that in the studied temperature range, there is a slight difference in the binding constant and the dissociation constant of the rosuvastatin-HAS complex. Conclusion: According to results obtained from multi-spectroscopic methods,SPR and molecular docking it can be concluded that, rosuvastatin can bind to human serum albumin and distributed throughout the body.