title: ANTI-INFLAMMATORY AND ANTIOXIDANT ACTIVITY OF 8-METHOXY-1,3-DIMETHYL-2,6-DIOXO-PURIN-7-YL DERIVATIVES WITH TERMINAL CARBOXYLIC, ESTER OR AMIDE MOIETIES IN ANIMAL MODELS.
abstract: The previous studies in a series of 8-methoxy-1,3-dimethyl-2,6-dioxo-purin-7-yl derivatives revealed their analgesic properties. We extended the study with these compounds in aim to assess their impact on inflammatory process. For this purpose we used: the zymosan-induced peritonitis and the carrageenan-induced edema model. Furthermore, the antioxidant activity of the investigated compounds by the FRAP assay was determined. For the most active derivatives from evaluated series their influence on plasma TNF-α level was also tested in vivo. All investigated purine-2,6-dione derivatives 1-11 decreased neutrophils count and inhibited intensity of early vascular permeability. Furthermore, all evaluated compounds reduced the volume of edema caused by subcutaneous injection of carrageenan. Derivatives 1 (with ester moiety), 3 and 4 (with carboxylic group) showed the highest activity in the zymosan-induced peritonitis. In addition, a significant inhibition of plasma TNF-α level in rats with endotoxemia was observed following intraperitoneal administration of these compounds. In turn, compounds 6 and 8-11 containing amide moiety showed the greatest anti-inflammatory (antiedematous) effect in the carrageenan-induced paw edema model. All compounds did not show significant antioxidant properties. The present studies revealed that the presented purine-2,6-dione derivatives exhibit a significant anti-inflammatory activity and this effect may result from their ability to lower TNF-α level.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.forename: Grazyna
authors.initials: G
authors.lastname: Chłon-Rzepa
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Wyska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Pociecha
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002351:Carrageenan; D019446:Endotoxemia / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D011687:Purines; D014409:Tumor Necrosis Factor-alpha; D002351:Carrageenan