Indomethacin Increases Quercetin Affinity for Human Serum Albumin: A Combined Experimental and Computational Study and Its Broader Implications.

Hrvoje Rimac,Mirza Bojić,Robert Vianello,Tana Tandarić

doi:10.3390/ijms21165740

Abstract

Human serum albumin (HSA) is the most abundant carrier protein in the human body. Competition for the same binding site between different ligands can lead to an increased active concentration or a faster elimination of one or both ligands. Indomethacin and quercetin both bind to the binding site located in the IIA subdomain. To determine the nature of the HSA-indomethacin-quercetin interactions, spectrofluorometric, docking, molecular dynamics studies, and quantum chemical calculations were performed. The results show that the indomethacin and quercetin binding sites do not overlap. Moreover, the presence of quercetin does not influence the binding constant and position of indomethacin in the pocket. However, binding of quercetin is much more favorable in the presence of indomethacin, with its position and interactions with HSA significantly changed. These results provide a new insight into drug-drug interactions, which can be important in situations when displacement from HSA or other proteins is undesirable or even desirable. This principle could also be used to deliberately prolong or shorten the xenobiotics’ half-life in the body, depending on the desired outcomes.

Highlights

Human serum albumin (HSA) is the most abundant protein in human plasma (60%, w/w) [1]
These results indicate that IND and QUE do not bind in the same location within the HSA
The results show that there is no significant difference in the IND position between the binary HSA-IND complex show that there is no significant difference in the IND position between the binary HSA-IND complex (IND is depicted in pink and HSA in brown) and the ternary HSA-IND-QUE complex (IND is depicted (IND is depicted in pink and HSA in brown) and the ternary HSA-IND-QUE complex (IND is in yellow and HSA in light blue) (Figure 5)

Summary

Introduction

Human serum albumin (HSA) is the most abundant protein in human plasma (60%, w/w) [1]. It is a 585-residue monomeric protein comprised of three homologous domains (I–III), each of which is composed of two subdomains (A and B) [2]. Flavonoids are a group of phenolic compounds, highly abundant in fruits and vegetables [9,10]. Apart from their antioxidative properties, which are the best described [11], they have a significant role in preventing cardiovascular diseases [12,13,14]

Methods

Results

Conclusion