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Indomethacin increases quercetin affinity for human serum albumin: a combined experimental and computational study and its broader implications

Rimac, Hrvoje; Tandarić, Tana; Vianello, Robert; Bojić, Mirza (2020) Indomethacin increases quercetin affinity for human serum albumin: a combined experimental and computational study and its broader implications. International Journal of Molecular Sciences, 21 (16). ISSN 1661-6596

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Abstract

Human serum albumin (HSA) is the most abundant carrier protein in 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 HSA-indomethacin- quercetin interactions, spectrofluorometric, docking, molecular dynamics studies, and quantum chemical calculations were performed. Results show that 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 xenobiotics’ half-life in the body, depending on the desired outcomes.

Item Type: Article
Uncontrolled Keywords: human serum albumin ; quercetin ; indomethacin ; pharmacokinetic interactions ; fluorescence spectroscopy ; docking ; molecular dynamics ; quantum chemistry
Subjects: NATURAL SCIENCES > Chemistry
BIOMEDICINE AND HEALTHCARE > Pharmacy
BIOMEDICINE AND HEALTHCARE > Pharmacy > Medical Biochemistry
Divisions: Division of Organic Chemistry and Biochemistry
Depositing User: Robert Vianello
Date Deposited: 20 Aug 2020 11:34
Last Modified: 10 Aug 2021 12:11
URI: http://fulir.irb.hr/id/eprint/5893
DOI: 10.3390/ijms21165740

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