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Keywords:
Acanthella cavernosa; anti-inflammatory; biosynthetic pathway; chiral separation; marine sponge; sesquiterpenoid
Abstract
One new aromadendrane-type sesquiterpenoid. namely ximaocavemosin P [(+)-!]. 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 (+)-l 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-a and CCL2 release in RAW 264.7 macrophages.
Introduction
Marine sponges of the genus Acanthella (class Demospongiae. order Halichondrida. family Axinellidae) are one of the most common marine invertebrates natively distributed throughout tropical and subtropical regions of the Indo-Pacific Ocean, in particular, the South China Sea [1]. They are well-known producers of various nitrogenous sesquiterpenes and diterpenes with characteristic isocyano, isothiocyano, and formamido functionalities [2-5]. Many of these secondary metabolites merit further investigation due to their intriguing structural diversity and wide spectra of biological activities ranging from antifeedant. antifouling, and cytotoxic to antibiotic effects [3.5.6]. Acanthella sponges have thus attracted much attention from marine natural products chemists and pharmacologists. The title animal is the most chemically studied species among the Acanthella sponges. Till now. more than 100 secondary metabolites belonging to sesquiterpenoids and diterpenes [7.8], alkaloids [9], and steroids [10], have been isolated and characterized.
In connection with our continuing studies of Chinese marine invertebrates to search for novel and bioactive secondary metabolites, we have recently studied the sponge A. cavernosa collected from Ximao Island of Hainan Province. China, resulting in the isolation of fifteen new nitrogenous sesquiterpenoids. exemplified by (+)-ximaocavernosin A (8) (Figure T) [11]. To accumulate more amounts of these sesquiterpenoids to perform more in-depth pharmacological screening, we carried out the chemical investigation of the same sample...