Novel inhibitors of mitochondrial respiratory chain: Endoperoxides from the marine tunicate Stolonica socialis

The Mediterranean tunicate Stolonica socialis contains a new class of power ful cytotoxic acetogenins, generically named stolonoxides. In this paper, w hich also details the isolation and chemical characterization of a minor co mponent (3a) of the tunicate extract, we report the potent inhibitory activ ity (IC50 < 1 muM) of stolonoxides (la and 3a) on mitochondrial electron tr ansfer. The compounds affect specifically the functionality of complex II ( succinate: ubiquinone oxidoreductase) and complex III (ubiquinol:cytochrome C oxidoreductase) in mammalian cells, thereby causing a rapid collapse of the whole energetic metabolism. This result, which differs from the propert ies of similar known products (e.g., 6), reflects the molecular features of stolonoxides.