Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa .

One new aromadendrane-type sesquiterpenoid, namely ximaocavernosin P [(+)- 1 ], and three new cadinane-type sesquiterpenoids, namely (+)-maninsigin D [(+)- 4 ], (+)- and (-)-ximaocavernosin Q [(+)- and (-)- 5 ], together with five related known ones [ 2 , 3 , (-)- 4 , 6 , and 7 ], were isolated from the Hainan sponge Acanthella cavernosa . Compounds 4 and 5 were isolated as racemic forms, which were further separated to the corresponding enantiomers [(+)- 4 /(-)- 4 and (+)- 5 /(-)- 5 ], respectively, by using chiral-phase HPLC. The structures of new compounds were elucidated by extensive spectroscopic analysis and comparison with the reported data. In addition, the absolute configuration of optically pure (+)- 1 and 2 were determined by time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculations or X-ray diffraction analysis. A plausible biosynthetic pathway of these sesquiterpenoids and their internal correlation were proposed and discussed. In an in vitro bioassay, (+)-aristolone ( 3 ) exhibited promising anti-inflammatory activity by the inhibition of LPS-induced TNF-α and CCL2 release in RAW 264.7 macrophages.