(4-Oxo-2-thioxothiazolidin-3-yl)acetic acids as potent and
selective aldose reductase inhibitors

J 2020

(4-Oxo-2-thioxothiazolidin-3-yl)acetic acids as potent and selective aldose reductase inhibitors

KUCEROVA-CHLUPACOVA, M., M. HALAKOVA, D. MAJEKOVA, Jakub TREML, J. STEFEK et. al.

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

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.192

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

Změněno: 24. 2. 2021 11:24, Mgr. Hana Hurtová

Anotace

V originále

(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.

Citovat

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. Dostupné z: https://dx.doi.org/10.1016/j.cbi.2020.109286.

@article{1745788,
   author = {KucerovaandChlupacova, M. and Halakova, M. and Majekova, D. and Treml, Jakub and Stefek, J. and Prnova, M.},
   article_location = {Clare},
   article_number = {109286},
   doi = {http://dx.doi.org/10.1016/j.cbi.2020.109286},
   keywords = {4-Oxo-2-thioxothiazolidin-3-yl)acetic acids; Rhodanine acetic acid; Aldose reductase inhibition; Cytotoxicity; Diabetes complication},
   language = {eng},
   issn = {0009-2797},
   journal = {Chemico-Biological Interactions},
   title = {(4-Oxo-2-thioxothiazolidin-3-yl)acetic acids as potent and selective aldose reductase inhibitors},
   url = {https://www.sciencedirect.com/science/article/pii/S0009279720313375},
   volume = {332},
   year = {2020}
}

TY  - JOUR
ID  - 1745788
AU  - Kucerova-Chlupacova, M. - Halakova, M. - Majekova, D. - Treml, Jakub - Stefek, J. - Prnova, M.
PY  - 2020
TI  - (4-Oxo-2-thioxothiazolidin-3-yl)acetic acids as potent and selective aldose reductase inhibitors
JF  - Chemico-Biological Interactions
VL  - 332
IS  - 109286
SP  - 1-7
EP  - 1-7
PB  - Elsevier Ireland Ltd.
SN  - 00092797
KW  - 4-Oxo-2-thioxothiazolidin-3-yl)acetic acids
KW  - Rhodanine acetic acid
KW  - Aldose reductase inhibition
KW  - Cytotoxicity
KW  - Diabetes complication
UR  - https://www.sciencedirect.com/science/article/pii/S0009279720313375
N2  - (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.
ER  -

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. \textit{Chemico-Biological Interactions}. Clare: Elsevier Ireland Ltd., 2020, roč.~332, č.~109286, s.~1-7. ISSN~0009-2797. Dostupné z: https://dx.doi.org/10.1016/j.cbi.2020.109286.

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