Fascioquinols A–F: bioactive meroterpenes from a deep-water southern Australian marine sponge, Fasciospongia sp.

Abstract

Chemical investigation of a southern Australian deep-water marine sponge, Fasciospongia sp., returned the new meroterpene sulfate fascioquinol A ( 1) together with a series of acid mediated hydrolysis/cyclization products, fascioquinols B ( 2), C ( 3) and D ( 4), and strongylophorine-22 ( 5). Additional co-metabolites include the new meroterpenes fascioquinol E ( 6) and fascioquinol F ( 8), together with the known sponge metabolite geranylgeranyl 1,4-hydroquinone ( 7). Structures were assigned to 1– 8 on the basis of detailed spectroscopic analysis, chemical interconversion, mechanistic and biosynthetic considerations, and literature comparisons. The known 1,4-hydroquinone 7 was identified as the dominant cytotoxic principle in the Fasciospongia sp. extract, with selective inhibitory activity against gastric adenocarcinoma (AGS, IC 50 8 μM) and neuroblastoma (SH-SY5Y, IC 50 4 μM) cell lines. By contrast, while the fascioquinols displayed little or no inhibitory activity towards human cell lines, 1 and 2 displayed promising Gram-positive selective antibacterial activity towards Staphylococcus aureus (IC 50 0.9–2.5 μM) and Bacillus subtilis (IC 50 0.3–7.0 μM).