Structure-activity relationships of 1'S-1'-acetoxychavicol acetate for inhibitory effect on NO production in lipopolysaccharide-activated mouse peritoneal macrophages.
1'S-1'-Acetoxychavicol acetate from the rhizomes of Alpinia galanga inhibited nitric oxide (NO) production in lipopolysaccharide-activated mouse peritoneal macrophages with an IC(50) value of 2.3 microM. To clarify the structure-activity relationship of 1'S-1'-acetoxychavicol acetate, various natural and synthetic phenylpropanoids and synthetic phenylbutanoids were examined, and the following structural requirements were clarified. (1) The para or ortho substitution of the acetoxyl and 1-acetoxypropenyl groups at the benzene ring was essential. (2) The S configuration of the 1'-acetoxyl group was preferable. (3) The presence of the 3-methoxyl group and disappearance of the 2'-3' double bond by hydrogenation reduced the activity. (4) The substitution of acetyl groups with propionyl or methyl groups reduced the activity. (5) Lengthening of the carbon chain between the 1'- and 2'-positions reduced the activity.
Matsuda
Hisashi
H
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Ando
Shin
S
Morikawa
Toshio
T
Kataoka
Shinya
S
Yoshikawa
Masayuki
M
D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry / Q000494:pharmacology; D001592:Benzyl Alcohols; D002244:Carbon / Q000737:chemistry; D005765:Gastrointestinal Agents / Q000737:chemistry / Q000494:pharmacology; D006865:Hydrogenation; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000378:metabolism*; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010654:Phenylbutyrates / Q000737:chemistry; D010666:Phenylpropionates / Q000737:chemistry; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D001592:Benzyl Alcohols; D005765:Gastrointestinal Agents; D008070:Lipopolysaccharides; D010654:Phenylbutyrates; D010666:Phenylpropionates; D013729:Terpenes; D009569:Nitric Oxide; D002244:Carbon; C047948:1'-acetoxychavicol acetate