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

• Main Authors: Beiko, Alona V., Kobzar, Oleksandr L., Kachaeva, Maryna V., Pilyo, Stepan G., Kozachenko, Olexandr P., Vovk, Andriy I.
• Format: Article
• Language: English
• Published: V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2023
• Subjects: rhodanine; 4-(furan-2-yl)benzoic acid; xanthine oxidase; inhibition; molecular docking; molecular dynamic; роданін; 4-(фуран-2-іл)бензойна кислота; ксантиноксидаза; інгібування; молекулярний докінг; молекулярна динаміка
• Online Access: https://bioorganica.com.ua/index.php/journal/article/view/75

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