Naslov
Formation of a ternary human serum albumin-indomethacin-quercetin complex and energy transfer

Autori
Rimac, Hrvoje

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Computational Chemistry Day 2019: Book of Abstracts / Babić, Darko - , 2019, 5-5

ISBN
978-953-6076-51-2

Skup
Computational Chemistry Day 2019

Mjesto i datum
Zagreb, Hrvatska, 11.05.2019

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
ljudski serumski albumin, indometacin, kvercetin, interakcije, spektrofluorimetrija, računalno modeliranje
(human serum albumin, indomethacin, quercetin, interactions, spectrofluorimetry, computer modeling)

Sažetak
Human serum albumin (HSA) is a plasma protein capable of binding and transporting a wide variety of ligands, both endogenous and exogenous. It serves as a depot for xenobiotics, prolonging their half-life in circulation and regulating their blood concentration. It consists of three domains (I–III), each of which is comprised of two subdomains (A and B) and the two most important binding sites for drugs are situated in subdomains IIA and IIIA, which are also called warfarin and benzodiazepine site, respectively (Figure 1.). Quercetin is a plant product abundant in every day diet, which has many salutary effects, of which its antioxidative, cardiovascular, and anticarcinogenic are the mostextensively studied. It binds to the IIA site of HSA, suggesting that its binding may cause displacement of drugs from these binding sites, leading to adverse effects. Indomethacin is a non-steroidal anti-inflammatory drug (NSAID), a derivative of methylated indole. It binds to the IIA HSA binding site >99% which means it can potentially interact with quercetin. In this work, spectrofluorimetry, docking and molecular dynamics simulations (MD) were used to obtain an insight of quercetin – indomethacin interactions in binding to HSA. Spectrofluorimetric data showed an increase of quercetin fluorescence in presence of indomethacin, which suggests stronger quercetin – HSA interactions. Further docking and MD simulations showed difference in interactions between quercetin and HSA in presence and absence of indomethacin, with indomethacin pushing quercetin deeper into the hydrophobic cleft and changing the nature of quercetin – HSA interactions from cation – π stacking to hydrogen bonding. The obtained results are consistent with the experimental fluorimetric data and provide additional insight into the xenobiotics – HSA binding mechanism.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Interdisciplinarne prirodne znanosti, Farmacija

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