4-(Фуран-2-іл)бензойні кислоти на основі роданіну як інгібітори ксантиноксидази

A series of rhodanine derivatives bearing 4-(furan-2-yl)benzoic acid moiety were synthesized and studied as inhibitors of xanthine oxidase. This enzyme is a known target for allopurinol and febuxostat used in the treatment of hyperuricemia, gout, and other diseases. The synthesized compounds with di...

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Збережено в:
Бібліографічні деталі
Дата:2023
Автори: Beiko, Alona V., Kobzar, Oleksandr L., Kachaeva, Maryna V., Pilyo, Stepan G., Kozachenko, Olexandr P., Vovk, Andriy I.
Формат: Стаття
Мова:English
Опубліковано: V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2023
Теми:
Онлайн доступ:https://bioorganica.com.ua/index.php/journal/article/view/75
Теги: Додати тег
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Назва журналу:Ukrainica Bioorganica Acta

Репозитарії

Ukrainica Bioorganica Acta
Опис
Резюме:A series of rhodanine derivatives bearing 4-(furan-2-yl)benzoic acid moiety were synthesized and studied as inhibitors of xanthine oxidase. This enzyme is a known target for allopurinol and febuxostat used in the treatment of hyperuricemia, gout, and other diseases. The synthesized compounds with different substituents in position 3 of the rhodanine ring showed in vitro inhibitory activities towards xanthine oxidase in a low micromolar concentration range. The 4-(furan-2-yl)benzoic acid derivative with a fragment of N-unsubstituted rhodanine was found to have the lowest IC50 value which does not depend on the presence of albumin or Tween-80 under the assay conditions. According to kinetic data, the rhodanine-based 4-(furan-2-yl)benzoic acid was a mixed-type inhibitor with the same affinity for the free enzyme and the enzyme-substrate complex. Molecular docking and molecular dynamic studies were performed to elucidate the binding mode of this compound in the active site of xanthine oxidase