Sulfonamide derivatives of styrylheterocycles as a potent inhibitor of COX-2-mediated prostaglandin E2 production.
The overproduction of prostaglandin E(2) (PGE(2)) plays an important role in a variety of pathophysiological processes including inflammation and carcinogenesis. Therefore, the modulation of PGE(2) production is a promising target in the design of chemotherapeutic agents. In the present study, the inhibitory effects of a series of styrylheterocycles having either a p-SO(2)NH(2) or p-SO(2)Me group on the production of cyclooxygenase-2-mediated PGE(2) were evaluated in lipopolysaccharide-stimulated RAW264.7 murine macrophages. Among the series of styrylheterocycle derivatives, (E)-4-(2-(thiophen-3-yl)vinyl)benzenesulfonamide exhibited a potent inhibitory activity, with an IC(50) value of 0.013 μM. The inhibitory activity against the overproduction of PGE(2) by the active compound was found to be due in part to the suppression of COX-2 mRNA expression.
College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Chaemin
C
Lim
Minhee
M
Lee
Eun-Jung
EJ
Park
Ran
R
Cho
Hyen-Joo
HJ
Park
Seong Jin
SJ
Lee
Heeyeong
H
Cho
Sang Kook
SK
Lee
Sanghee
S
Kim
D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
D006571:Heterocyclic Compounds; D012333:RNA, Messenger; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D015232:Dinoprostone