New jasmonate analogues as potential anti-inflammatory agents.
In an effort to develop new anti-inflammatory agents, methyl jasmonate analogues (2-20) were synthesized and evaluated for their inhibitory effects on the production of pro-inflammatory mediators (NO, IL-6, and TNF-alpha) in lipopolysaccharide (LPS)-activated RAW264.7 murine macrophage cells. The introduction of an enone functionality to the structure of a plant hormone (1) rendered the product (2) a significant anti-inflammatory activity. Analogues further derived from 2 (7, 9, 13, and 15) exhibited even more enhanced activity, and these compounds were much more potent than natural anti-inflammatory prostaglandins (PGA(1), PGA(2), and 15-deoxy-Delta(12,14)-PGJ(2)). Among them, compounds 9 and 15 showed the highest potency, while compounds 7 and 13 would be more desirable with respect to safety. This is the first study demonstrating the anti-inflammatory potential of jasmonate derivatives, and the present results suggest that alpha-haloenone jasmonates (7, 9, 13, and 15) may serve as potential anti-inflammatory leads.
Dang
Hung The
HT
College of Pharmacy, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of Korea.
Lee
Hye Ja
HJ
Yoo
Eun Sook
ES
Hong
Jongki
J
Bao
Baoquan
B
Choi
Jae Sue
JS
Jung
Jee H
JH
D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D054883:Oxylipins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000085:Acetates; D000893:Anti-Inflammatory Agents; D003517:Cyclopentanes; D015850:Interleukin-6; D008070:Lipopolysaccharides; D054883:Oxylipins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C072239:methyl jasmonate; D015230:Prostaglandin D2