Probing the potential toxicity of trimetazidine by characterizing its interaction with human serum albumin

Abstract

Since the small molecular drugs pharmacodynamics and pharmacokinetics could be affected by human serum albumin (HSA) transport, we used spectroscopic and molecular docking studies to investigate the interaction between HSA and the angina-prevention drug trimetazidine (TMZ). As shown by synchronous fluorescence spectroscopy, this interaction affects the microenvironment confirmation around tyrosine residues. The site-competitive experiments showed that TMZ had an affinity toward subdomain III A (site II) of HSA. The enthalpy and entropy changes (ΔH and ΔS), which were 37.75 and 0.197 K J mol-1, respectively, showed that the predominant intermolecular interactions stabilizing the TMZ-HSA combination are hydrophobic forces. According to FTIR research, the interaction between HSA and TMZ caused polypeptide carbonyl-hydrogen bonds to rearrange. Additionally, the HSA esterase enzyme activity was assessed, which revealed a decrease in activity with TMZ. Docking analysis confirmed the site-competitive experiments and thermodynamic results. Also, it showed that TMZ has strong affinity for binding to HSA and inserted into HSA subdomain III A (site II) with score of -12.65. This study demonstrated that TMZ interacted with HSA, and the structure and function of HSA were influenced by TMZ. This study could aid in understanding the pharmacokinetics of TMZ and provide basic data for safe use.