Exploring the interaction between lovastatin and its main metabolite with human serum albumin: Aplication of spectroscopic and molecular modeling methods

Abstract

Introduction: Albumin is the most important plasma protein that affects the pharmacokinetic and pharmacodynamic properties of drugs. Studying the interactions between albumin and drugs provides useful information in designing new drugs with better properties. Objective: In this study, the interaction of lovastatin and its active metabolite with albumin was investigated using different spectroscopic and molecular modeling methods. Methods: The interaction between lovastatin and its active metabolite with human serum albumin is investigated using various spectroscopic methods and the parameters required for analyzing the interaction by Stern-Valmer equations are investigated. Results: The results of absorption and emission spectroscopy studies indicate the interaction between lovastatin and its active metabolite with human serum albumin. The interaction between metabolites is stronger than the drug itself. Lovastatin-induced quenching is a static type and quenching of its active metabolite is a hybrid type. The results of FT-IR studies indicate a change in the secondary structure of albumin in the presence of these two ligands, these changes being more in the presence of the active metabolite than the prodrug. Based on the results of molecular docking, the major force involved in the interaction is hydrogen bonding. Fluorimetric studies in the presence of site markers indicate that lovastatin tends to bind to both the ⅡA and ⅢA binding sites and the active metabolite to the ⅢA binding site. Conclusion: According to the obtained data, it can be concluded that lovastatin and its active metabolite bind to human serum albumin. But the active metabolite is more likely to bind.