Non-phenolic linear diarylheptanoids from Curcuma xanthorrhiza: a novel type of topical anti-inflammatory agents: structure-activity relationship.
The topical anti-inflammatory activity of three non-phenolic linear 1,7-diarylheptanoids, previously isolated from a Thai medicinal plant, Curcuma xanthorrhiza (Zingiberaceae) and four new semi-synthetic derivatives of the naturally occurring compounds were assessed in the murine model of ethyl phenylpropiolate-induced ear edema. The naturally occurring compound 1E,3E,1,7-diphenylheptadien-5-one (6) exerted the most potent anti-inflammatory activity, with an ID50 value of similar magnitude to that of the reference drug oxyphenbutazone (67 vs. 46 micrograms/ear, respectively). None of the semi-synthetic diarylheptanoids was more active than 6. The chemical structures and pharmacological data of the natural and semi-synthetic derivatives identified a distinct structure-activity relationship. The degree of unsaturation in positions 1 and 3, and the nature of the oxygenated functional group in position 5 of the C7-chain were found to play significant roles in determining the observed in vivo activity. Based on these findings, the non-phenolic linear 1,7-diarylheptanoids-are proposed to represent a novel class of topical anti-inflammatory agents.
Claeson
P
P
Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
Pongprayoon
U
U
Sematong
T
T
Tuchinada
P
P
Reutrakul
V
V
Soontornsaratune
P
P
Taylor
W C
WC
D000480:Alkynes; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D001210:Asia, Southeastern; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006536:Heptanes / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D007249:Inflammation; D008297:Male; D015394:Molecular Structure; D010113:Oxyphenbutazone / Q000494:pharmacology; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D000480:Alkynes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006536:Heptanes; C015202:ethylphenylpropiolate; D010113:Oxyphenbutazone