In vitro stability and in vivo anti-inflammatory efficacy of synthetic jasmonates.
A chlorinated methyl jasmonate analog (J7) was elaborated as an in vitro anti-inflammatory lead. However, its in vitro efficacy profile was not reproduced in a subsequent in vivo evaluation, presumably due to its rapid enzymatic hydrolysis in a biological system. In an attempt to improve the metabolic stability of the lead J7 by replacement of its labile methyl ester with reasonable ester groups, several analogs resistant to enzymatic hydrolysis were synthesized. In vivo evaluation of the stability-improved analogs showed that these compounds displayed higher efficacy than the lead J7, suggesting that these new jasmonate analogs may serve as potential anti-inflammatory leads.
College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
Hung The
HT
Dang
Yoon Mi
YM
Lee
Gyeoung Jin
GJ
Kang
Eun Sook
ES
Yoo
Jongki
J
Hong
Sun Mee
SM
Lee
Sang Kook
SK
Lee
Yuna
Y
Pyee
Hwa-Jin
HJ
Chung
Hyung Ryong
HR
Moon
Hyung Sik
HS
Kim
Jee H
JH
Jung
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D054883:Oxylipins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D003517:Cyclopentanes; D005231:Fatty Acids, Unsaturated; D054883:Oxylipins; C555027:methyl 5-chloro-4,5-didehydrojasmonate; D009569:Nitric Oxide; C011006:jasmonic acid