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, (+)-7β-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), (+)-7β-acetoxy-3,13-clerodadiene-16,15-olide-18-oic acid (4), (+)-7β-acetoxy-16-hydroxy-3,13-clerodadiene-16,15-olide-18-oic acid (5), β-caryophyllene oxide (6), clovane-2β,9β-diol (7), and caryolane-1,9β-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 μM.