Anti-inflammatory constituents of the red alga Gracilaria verrucosa and their synthetic analogues.
A chemical study on the anti-inflammatory components of the red alga Gracilaria verrucosa led to the isolation of new 11-deoxyprostaglandins ( 1- 4), a ceramide ( 5), and a C 16 keto fatty acid ( 6), along with known oxygenated fatty acids ( 7- 14). Their structures were elucidated on the basis of NMR and MS data. The absolute configurations of compounds 1- 5 were determined by Mosher's method. The anti-inflammatory activity of the isolated compounds ( 1- 14) was evaluated by determining their inhibitory effects on the production of pro-inflammatory mediators (NO, IL-6, and TNF-alpha) in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells. Compounds 9 and 10 exhibited the most potent activity. In the evaluation of these two compounds and derivatized analogues ( 15- 40), the anti-inflammatory activity was enhanced in some synthetic analogues. These enone fatty acids were investigated as potential anti-inflammatory leads for the first time.
Dang
Hung The
HT
College of Pharmacy, Pusan National University, Busan, Korea.
Lee
Hye Ja
HJ
Yoo
Eun Sook
ES
Shinde
Pramod B
PB
Lee
Yoon Mi
YM
Hong
Jongki
J
Kim
Dong Kyoo
DK
Jung
Jee H
JH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005227:Fatty Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D044724:Gracilaria / Q000737:chemistry*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D015850:Interleukin-6 / Q000096:biosynthesis; D007723:Korea; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis; D011458:Prostaglandins E / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005227:Fatty Acids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011458:Prostaglandins E; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide