Di- and sesqui-terpenoids isolated from the pods of Sindora sumatrana and their potential to inhibit lipopolysaccharide-induced nitric oxide production.
Activity-guided fractionation of the n-hexane and CHCl3-soluble fractions of Sindora sumatrana using a bioassay based on the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) in murine macrophage RAW 264.7 cells led to the isolation of the known compound, (+)-7beta-acetoxy-15,16-epoxy-3,13(16),14-clerodatriene-18-oic acid (2) as an active constituent. In addition, a new trans-clerodane diterpenoid, (+)-2-oxokolavenic acid (1), together with six known compounds, (+)-3,13-clerodadiene-16,15-olide-18-oic acid (3), (+)-7beta-acetoxy-3,13-clerodadiene-16,15-olide-18-oic acid (4), (+)-7beta-acetoxy-16-hydroxy-3,13-clerodadiene-16,15-olide-18-oic acid (5), beta-caryophyllene oxide (6), clovane-2beta,9beta-diol (7), and caryolane-1,9beta-diol (8) were isolated and found to be inactive. The structure of compound 1 was determined using physical and spectroscopic methods such as 1D and 2D-NMR experiments. The known compounds 2-8 were identified by the spectroscopic data and by comparison with the published values. Of eight isolates (1-8), only compound 2 exhibited an iNOS inhibitory activity with IC50 value of 51.6 microM.
Jang
Dae Sik
DS
Division of Molecular Life Sciences, Ewha Womans University, Seoul 120-750, Korea.
Min
Hye-Young
HY
Jeong
Yeon-Hee
YH
Lee
Sang Kook
SK
Seo
Eun-Kyoung
EK
D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D007887:Fabaceae; D005638:Fruit; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D010936:Plant Extracts; D013729:Terpenes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse