Scalarane Sesterterpenoids Isolated from the Marine Sponge Hyrtios erectus and their Cytotoxicity.

Eighteen scalarane sesterterpenoids ( 1 - 18 ), including eight new derivatives ( 1 - 8 ), were isolated from the sponge Hyrtios erectus (family Thorectidae), the extract of which showed cytotoxicity against the HeLa and MCF-7 cell lines. Of the new derivatives, six compounds ( 1 - 6 ) were found to contain a γ-hydroxybutenolide moiety capable of reversible stereoinversion at the hydroxylated carbon center. Under the influence of other adjacent functional groups, each derivative exhibited a different stereochemical behavior, which was fully deduced by ROESY experiments. All the isolated compounds were examined for their cytotoxicity by MTS assay using staurosporine as a positive control (IC 50 0.18 and 0.13 μΜ against HeLa and MCF-7 cells, respectively), and they were found to show weak growth inhibitory activities against HeLa and MCF-7 cells, with a minimal IC 50 value of 20.0 μΜ. The compounds containing a γ-hydroxybutenolide moiety ( 1 - 3 , 10 , 12 ) showed cytotoxicity, with IC 50 values ranging from 24.3 to 29.9 μΜ, and the most potent derivative was heteronemin ( 16 ). Although the cytotoxicities of isolated compounds were insufficient to discuss the structure-activity relationship, this research could contribute to expanding the structural diversity of scalaranes and understanding the stereochemical behavior of γ-hydroxybutenolides.