Study of Interactions between Amlodipine and Quercetin on Human Serum Albumin: Spectroscopic and Modeling Approaches.

Zuzana Vaneková,José Toca-Herrera,Lukáš Hubčík,Pavel Mučaji,Milan Nagy,Paul Furtműller,Jindra Valentová

doi:10.3390/molecules24030487

Abstract

The aim of this study was to analyze the binding interactions between a common antihypertensive drug (amlodipine besylate—AML) and the widely distributed plant flavonoid quercetin (Q), in the presence of human serum albumin (HSA). Fluorescence analysis was implemented to investigate the effect of ligands on albumin intrinsic fluorescence and to define the binding and quenching properties. Further methods, such as circular dichroism and FT-IR, were used to obtain more details. The data show that both of these compounds bind to Sudlow’s Site 1 on HSA and that there exists a competitive interaction between them. Q is able to displace AML from its binding site and the presence of AML makes it easier for Q to bind. AML binds with the lower affinity and if the binding site is already occupied by Q, it binds to the secondary binding site inside the same hydrophobic pocket of Sudlow’s Site 1, with exactly the same affinity. Experimental data were complemented with molecular docking studies. The obtained results provide useful information about possible pharmacokinetic interactions upon simultaneous co-administration of the food/dietary supplement and the antihypertensive drug.

Highlights

IntroductionHuman serum albumin (HSA) is the most prevalent protein in human plasma, constituting ~60%
Human serum albumin (HSA) is the most prevalent protein in human plasma, constituting ~60%of the total plasma protein content
Intrinsic fluorescence of proteins caused by aromatic amino acid residues, namely tryptophan (Trp), tyrosine (Tyr), and phenylalanine is caused by aromatic amino acid residues, namely tryptophan (Trp), tyrosine (Tyr), and (Phe)

Summary

Introduction

Human serum albumin (HSA) is the most prevalent protein in human plasma, constituting ~60%. HSA and its ability to bind and transport a wide range of molecules (e.g., drugs, metabolites, fatty acids, etc.) play a key role in drug distribution. HSA in the presence of multiple ligands creates a complex system, where several molecules. Molecules 2019, 24, 487 may or may not compete to bind to the same binding site. Since only the free fraction of the total amount of drug is responsible for the therapeutic effect, these competitive displacement interactions should be considered when multiple [5]. System, where several molecules may HSA in the presence ofadministering multiple ligands createsdrugs a complex Since only the free fraction of the total amount of drug is responsible for the therapeutic effect, these competitive displacement interactions should be considered when multiple [5]. system, where several molecules may HSA in the presence ofadministering multiple ligands createsdrugs a complex

Objectives

Methods

Results

Conclusion