Globostelletins A–I, cytotoxic isomalabaricane derivatives from the marine sponge Rhabdastrella globostellata

Nine new isomalabaricane-derived natural products, globostelletins A–I (1–9), were isolated from the marine sponge Rhabdastrella globostellata, together with jaspolides F (10), rhabdastrellic acid-A (11), (−)-stellettin E (12), stellettins C (13) and D (14). The structures of these compounds were determined on the basis of extensive spectroscopic analyses and by comparison with the reported data in the literature. The inhibitory activities of compounds 1–12 against human tumor cell lines were evaluated, and their structure–activity relationships were discussed. In addition, rhabdastrellic acid-A (11) showed potent inhibition against HL-60 cells, and it induced the apoptosis of HL-60 cells in M/G2 phase. The mechanism of 11 targeting the ubiquitin-proteasome system, including the regulation of ChT-L and T-L target proteins is discussed.

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