Anti-inflammatory and Antimalarial Meroterpenoids from the New Zealand Ascidian Aplidium scabellum

Abstract

Bioassay-directed fractionation of an extract of the New Zealand ascidian Aplidium scabellum has afforded the anti-inflammatory secondary metabolite 2-geranyl-6-methoxy-1,4-hydroquinone-4-sulfate (1) and a family of pseudodimeric meroterpenoids scabellones A (2)-D (5). The benzo[c]chromene-7,10-dione scaffold contained within scabellones A-D is particularly rare among natural products. The structures were elucidated by interpretation of NMR data. Scabellone B was also identified as a moderately potent, nontoxic inhibitor of Plasmodium falciparum.

Naturally Occurring and Synthetic Agents as Potential Anti-Inflammatory and Immunomodulants

“…The benzo[c]chromene-7,10-dione scaffold contained within scabellones A-D is particularly rare among natural products. Scabellone B was also identified as a moderately potent, nontoxic inhibitor of Plasmodium falciparum [147] A phytochemical investigation of Inula falconeri, a plant endemic to the Himalayas, afforded 10 new sesquiterpenoids and 26 known sesquiterpene lactones, including those bearing guaiane, pseudoguaiane, xanthane, eudesmane, germacrane, rare secocaryophyllane, chromolaevane, and carabrane frameworks. All the isolates were assessed for their inhibitory effects against LPS-induced nitric oxide production in RAW264.7 macrophages.…”

Quinone and Hydroquinone Metabolites from the Ascidians of the Genus Aplidium

“…Direct comparison of the 1 H and 13 C chemical shifts of the aromatic ring signals of 17 with a synthetic derivative of 17 (compound which had a hydroxyl group at C-4 instead of the sulfate) allow Chan and co-worker to identified an upfield shift of C-4 and downfield shifts of C-3 and C-5 in the 13 C-NMR spectrum and downfield shifts of H-3 and H-5 in the 1 H-NMR spectrum which were consistent with the placement of the sulfate group at the C-4 [17]. …”

“…Davis and co-workers [16] reported a simple and versatile route to 1,4-benzoquinones based on the Claisen rearrangement, and applied to the synthesis of verapliquinones A and B, which had not previously been synthesized [16]. Chan and co-workers (2011) also reported verapliquinone A from A. scabellum [17]. …”

“…To determine the effect of different treatments on cell survival, drug-treated neutrophils were stained with the fluorescent markers for necrosis (propidium iodide) and apoptosis (Annexin V-FITC), and analyzed by flow cytometry. Treatment with 17 had no effect on neutrophil viability, but the results indicated that 17 did inhibit neutrophil superoxide production [17]. …”

“…Chan et al , 2011 [17], have described the isolation of the pseudodimeric meroterpenoid scabellones A–D ( 41 – 44 ) (Figure 7). Scabellone B ( 42 ) was able to inhibit the superoxide production by PMA-stimulated human neutrophils in vitro , with an IC 50 of 125 μM.…”