Analgesic and anti-inflammatory activity of 7-substituted purine-2,6-diones

• Published in: Pharmacological reports 2014-12, Vol.66 (6), p.996-1002
• Main Authors: Zygmunt, Małgorzata, Chłoń-Rzepa, Grażyna, Sapa, Jacek
• Format: Article
• Language: English
• Subjects: 2,6-Dioxo-purin-7-yl derivatives; Analgesic; Analgesics - chemistry; Analgesics - pharmacology; Animals; Anti-inflammatory activities; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Carrageenan - toxicity; Disease Models, Animal; Drug Safety and Pharmacovigilance; Edema - drug therapy; Formaldehyde - toxicity; Original Research Article; Pharmacotherapy; Pharmacy; Phosphodiesterase; Purines - chemistry; Purines - pharmacology; Rolipram - pharmacology; Theophylline - pharmacology
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/j.pharep.2014.06.015

In an effort to develop new analgesic and anti-inflammatory agents, we determined a series of 7-substituted purine-2,6-diones. The obtained compounds (1–6) were evaluated pharmacologically in four in vivo models: the writhing syndrome, the formalin tests, the carrageenan-induced edema model and the zymosan-induced peritonitis. The influence of the investigated compounds on the phosphodiesterase (PDE) and PDE4B activity was also determined. In addition, determination of the antioxidant activity was determined by the FRAP assay. A majority of the tested compounds showed a significant analgesic and anti-inflammatory activity. The strongest analgesic and anti-inflammatory effect was observed for 1 and 2. The active compound 1 was more efficient than theophylline in inhibiting the PDE and more efficient than rolipram in inhibiting the PDE4B activity. The tested compounds did not show significant antioxidant properties. Active compounds (1–6) inhibited the PDE activity, while compound 1 significantly inhibited the PDE4B activity, what may suggest that this mechanism may be involved in their analgesic/anti-inflammatory properties.