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 (IC₅₀ 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 IC₅₀ value of 20.0 μΜ. The compounds containing a γ-hydroxybutenolide moiety (1-3, 10, 12) showed cytotoxicity, with IC₅₀ 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.