Open AccessInhibition of prostaglandin E 2 production by 2′‐hydroxychalcone derivatives and the mechanism of action
Author(s) -
Kim Yong Pil,
Ban Hyun Seung,
Lim Soon Sung,
Kimura Natsuko,
Jung Sang Hoon,
Ji Jun,
Lee Sanghyun,
Ryu Nama,
Keum Sam Rok,
Shin Kuk Hyun,
Ohuchi Kazuo
Publication year - 2001
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/0022357011776595
Subject(s) - prostaglandin e2 , cyclooxygenase , ic50 , arachidonic acid , chemistry , prostaglandin , western blot , mechanism of action , biochemistry , activator (genetics) , chalcone , pharmacology , prostaglandin e , enzyme , stereochemistry , in vitro , biology , receptor , endocrinology , gene
The effects of 14 synthetic 2′‐hydroxychalcone derivatives on prostaglandin E 2 (PGE 2 ) production in rat peritoneal macrophages stimulated by the protein kinase C activator, 12‐O‐tetradecanoylphorbol 13‐acetate (TPA), were examined to clarify the structure‐activity relationship. 2′,4‐Dihydroxy‐4′‐methoxychalcone (compound 3), 2′,4‐dihydroxy‐6′‐methoxychalcone (compound 8 ) and 2′‐hydroxy‐4′‐methoxychalcone (compound 9 ) suppressed PGE 2 production more potently than the other compounds. The IC50 (50 % Inhibitory concentration) value for compounds 3, 8 and 9 was calculated to be 3 μ. The activity of cyclooxygenase (COX)‐1 was inhibited slightly by compound 9 , but that of COX‐2 was not inhibited. At concentrations that inhibited the production of PGE 2 , compound 9 had no effect on the release of radioactivity from [ 3 H]arachidonic acid‐labelled macrophages stimulated by TPA. Western‐blot analysis revealed that the induction of COX‐2 protein by TPA was inhibited by compound 9 in parallel with the inhibition of PGE 2 production. Compounds 3 and 8 had similar effects. These findings suggest that 4′‐methoxyl and 6′‐methoxyl groups are required for the expression of more potent inhibitory activity against PGE 2 production, and that the inhibition of PGE 2 production by these 2′‐hydroxychalcone derivatives is due to the inhibition of TPA‐induced COX‐2 protein expression.