title: Analgesic and anti-inflammatory activity of 7-substituted purine-2,6-diones.
abstract: BACKGROUND
  In an effort to develop new analgesic and anti-inflammatory agents, we determined a series of 7-substituted purine-2,6-diones.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland. Electronic address: gogol67@interia.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Chłoń-Rzepa
authors.affiliation: Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan / Q000633:toxicity; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy; D005557:Formaldehyde / Q000633:toxicity; D011687:Purines / Q000737:chemistry / Q000494:pharmacology*; D020889:Rolipram / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D011687:Purines; D005557:Formaldehyde; D002351:Carrageenan; D013806:Theophylline; D020889:Rolipram
keywords: 2,6-Dioxo-purin-7-yl derivatives; Analgesic; Anti-inflammatory activities; Phosphodiesterase