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.
