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

• Datum: 2023
• Автори та афіліації: Alona V. Beiko — V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine; Oleksandr L. Kobzar — V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine; Maryna V. Kachaeva — V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine; Stepan G. Pilyo — V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine; Olexandr P. Kozachenko — V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine; Andriy I. Vovk — V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine
• Ключові слова: keywords
• Hauptverfasser: Beiko, Alona V., Kobzar, Oleksandr L., Kachaeva, Maryna V., Pilyo, Stepan G., Kozachenko, Olexandr P., Vovk, Andriy I.
• Format: Artikel
• Sprache: Englisch
• Veröffentlicht: V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2023
• Schlagworte: роданін; 4-(фуран-2-іл)бензойна кислота; ксантиноксидаза; інгібування; молекулярний докінг; молекулярна динаміка
• Online Zugang: https://bioorganica.com.ua/index.php/journal/article/view/75
• Назва журналу: Ukrainica Bioorganica Acta

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