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.