Bioactive Molecules Isolated from the Sea Slug Pleurobranchus forskalii

The sea slug Pleurobranchus forskalii (class Gastropoda, order Notaspidea, family Pleurobranchidae) is widely distributed in temperate, shallow, subtidal areas around the Indo-Pacific and Mediterranean seas. It belongs to a family of shell-less mollusks that have been known to be opportunistic carnivores, and scavenge on a variety of other invertebrates, such as sponges and ascidians. Although these physically defenseless mollusks are believed to secrete bioactive chemicals for their protection, and are, therefore, a vast resource of secondary metabolites, there have only been a limited number of studies on the chemical components of P. forskalii.

A macrocylic dodecapeptide, cycloforskamide, was isolated from the sea slug, P. forskalii, collected off Ishigaki Island, Japan. Its planar structure was deduced by extensive NMR analyses, and was further confirmed by MS/MS fragmentation analyses. Finally, the absolute configuration was determined by total hydrolysis and chiral phase-gas chromatographic analysis. This novel peptide containing twelve amino acids and three thiazoline heterocycles, exhibits cytotoxicity against murine leukemia P388 cells, with an IC₅₀ of 6.85 µg/mL. Furthermore, an ergot alkaloid peptide, ergosinine, which has, so far, been isolated only from terrestrial higher plants and fungi, has also been found in P. forskalii. This is the first report of the isolation of an ergopeptine from marine life, and thus the known geographical extent of ergot alkaloids now includes both terrestrial and aquatic organisms.