Cyperane-Type And Related (Nor)Sesquiterpenoids From The Root Bark Of Acanthopanax Gracilistylus And Their Inhibitory Effects On Nitric Oxide Production

An enantiomeric pair of rare cyperane-type sesqui-terpenoids, (+)- and (-)-gracilistones C (1a, 1b), together with a novel norsesquiterpenoid, gracilistone D (2), bearing a bicyclic lactone system were isolated from the root bark of Acanthopanax gracilistylus using LC-MS-IT-TOF analyses. The structures and absolute configurations of 1a, 1b, and 2 were elucidated by 1D and 2D NMR spectroscopy, X-ray diffraction, and ECD spectroscopic methods. Intermediate 1b suggests a possible biosynthesis process involving compound 2. The bioassay results showed that compounds 1a, 1b, and 2 exhibited significant inhibitory effects against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells, with IC50 values of 7.7 +/- 0.6, 6.8 +/- 1.5, and 2.6 +/- 0.4 mu M, respectively. Additional docking analyses provided some perspective of this activity in human inducible nitric oxide synthase.