KUCEROVA-CHLUPACOVA, M., M. HALAKOVA, D. MAJEKOVA, Jakub TREML, J. STEFEK a M. PRNOVA. (4-Oxo-2-thioxothiazolidin-3-yl)acetic acids as potent and selective aldose reductase inhibitors. Chemico-Biological Interactions. Clare: Elsevier Ireland Ltd., 2020, roč. 332, č. 109286, s. 1-7. ISSN 0009-2797. doi:10.1016/j.cbi.2020.109286.
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Základní údaje
Originální název (4-Oxo-2-thioxothiazolidin-3-yl)acetic acids as potent and selective aldose reductase inhibitors
Autoři KUCEROVA-CHLUPACOVA, M., M. HALAKOVA, D. MAJEKOVA, Jakub TREML (203 Česká republika, domácí), J. STEFEK a M. PRNOVA.
Vydání Chemico-Biological Interactions, Clare, Elsevier Ireland Ltd. 2020, 0009-2797.
Další údaje
Originální jazyk angličtina
Typ výsledku Článek v odborném periodiku
Obor 30104 Pharmacology and pharmacy
Stát vydavatele Irsko
Utajení není předmětem státního či obchodního tajemství
WWW URL
Impakt faktor Impact factor: 3.723 v roce 2019
Kód RIV RIV/00216224:14160/20:00118249
Organizační jednotka Farmaceutická fakulta
Doi http://dx.doi.org/10.1016/j.cbi.2020.109286
UT WoS 000595953700005
Klíčová slova anglicky 4-Oxo-2-thioxothiazolidin-3-yl)acetic acids; Rhodanine acetic acid; Aldose reductase inhibition; Cytotoxicity; Diabetes complication
Štítky rivok, ÚMF
Příznaky Mezinárodní význam, Recenzováno
Změnil Změnila: Mgr. Hana Hurtová, učo 244985. Změněno: 24. 2. 2021 11:24.
Anotace
(4-Oxo-2-thioxothiazolidin-3-yl)acetic acids exhibit a wide range of pharmacological activities. Among them, the only derivative used in clinical practice is the aldose reductase inhibitor epalrestat. Structurally related compounds, [(5Z)-(5-arylalkylidene-4-oxo-2-thioxo-1,3-thiazolidin-3-yl)]acetic acid derivatives were prepared previously as potential antifungal agents. This study was aimed at the determination of aldose reductase inhibitory action of the compounds in comparison with epalrestat and evaluation of structure-activity relationships (SAR). The aldose reductase (ALR2) enzyme was isolated from the rat eye lenses, while aldehyde reductase (ALR1) was obtained from the kidneys. The compounds studied were found to be potent inhibitors of ALR2 with submicromolar IC50 values. (Z)-2-(5-(1-(5-butylpyrazin-2-yl)ethylidene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid (3) was identified as the most efficacious inhibitor (over five times more potent than epalrestat) with mixed-type inhibition. All the compounds also exhibited low antiproliferative (cytotoxic) activity to the HepG2 cell line. Molecular docking simulations of 3 into the binding site of the aldose reductase enzyme identified His110, Trp111, Tyr48, and Leu300 as the crucial interaction counterparts responsible for the high-affinity binding. The selectivity factor for 3 in relation to the structurally related ALR1 was comparable to that for epalrestat. SAR conclusions suggest possible modifications to improve further inhibition efficacy, selectivity, and biological availability in the group of rhodanine carboxylic acids.
VytisknoutZobrazeno: 18. 5. 2021 15:15