5-Заміщені N-(9Н-пурин-6-іл)-1,2-оксазол-3-карбоксаміди як інгібітори ксантиноксидази

• Datum: 2020
• Автори та афіліації: Oksana V. Muzychka — V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine; Oleksandr L. Kobzar — V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine; Oleh V. Shablykin — V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine; Volodymyr S. Brovarets — V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine; Andriy I. Vovk — V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine
• Ключові слова: keywords
• Hauptverfasser: Muzychka, Oksana V., Kobzar, Oleksandr L., Shablykin, Oleh V., Brovarets, Volodymyr S., 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 2020
• Schlagworte: N-(9Н-пурин-6-іл)-1,2-оксазол-3-карбоксаміди; синтез; біоактивність; ксантиноксидаза
• Online Zugang: https://bioorganica.com.ua/index.php/journal/article/view/4
• Назва журналу: Ukrainica Bioorganica Acta

Synthetic 6-substituted purine derivatives are known to exhibit diverse bioactivity. In this paper, a series of N-(9H-purin-6-yl)-1,2-oxazole-3-carboxamide derivatives were synthesized and evaluated in vitro against xanthine oxidase, an enzyme of purine catabolism. The introduction of aryl substituent at position 5 of the oxazole ring was found to increase the inhibition efficiency. Some of the inhibitors containing 5-substituted isoxazole and purine moieties were characterized by IC50 values in the nanomolar range. According to the kinetic data, the most active N-(9H-purin-6-yl)-5-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,2-oxazole-3-carboxamide demonstrated a competitive type of inhibition with respect to the enzyme-substrate. Molecular docking was carried out to elucidate the mechanism of enzyme-inhibitor complex formation. The data obtained indicate that xanthine oxidase may be one of the possible targets for the bioactive purine carboxamides.