title: Styrylquinazolines: a new class of inhibitors on prostaglandin E2 production in lipopolysaccharide-activated macrophage cells.
abstract: A series of styrylquinazoline derivatives (2a-k) were prepared and evaluated for their inhibiton of prostaglandin E(2) (PGE(2)) production by cyclooxygenase-2 (COX-2). The latter was induced by lipopolysaccharide-stimulated macrophage cells RAW264.7. 3', 4'-Dihydroxylated styrylquinazolines (2a-c), 3'-hydroxylated styrylquinazolines (2h, 2i), and 3'-acetoxy-styrylquinazolines (2j, 2k) exhibited good inhibitory effects of PGE(2) production by COX-2 with a range of IC(50) values of 1.19 approximately 3.56 microM. The potencies were comparable or better than that of the representative stilbene resveratrol (IC(50) = 3.07 microM). These results indicate that styrylquinazolines can be considered as potential resveratrol analogues in the modulation of prostaglandin production by COX-2.
authors.affiliation: Medicinal Chemistry Research Center, Life Sciences Division, Korea Institute of Science and Technology, Seoul 130-650, Korea.
authors.forename: Jang Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Min
authors.forename: Sun Suk
authors.initials: SS
authors.lastname: Kim
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Lee
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D002460:Cell Line; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry; D013343:Styrenes / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D007527:Isoenzymes; D008070:Lipopolysaccharides; D011799:Quinazolines; D013267:Stilbenes; D013343:Styrenes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D000077185:Resveratrol