Abstract
Many interesting bioactive compounds have been obtained from ascidians (tunicates). Some ascidians live with photosynthetic prochlorons at the shallow water environments and some with bacteria of thioautotrophs. These associations with diverse microorganisms raised the question of the origins of the bioactive compounds whether from animal cells or associated microorganisms. Aromatic alkaloids possessing polysulfide structures have been isolated from ascidians of the genera Lissoclinum, Eudistoma, and Polycitor that the species do not have prochlorons. More than ten monomeric cyclic polysulfides and four dimeric polysulfides have been reported. These compounds presented the various biological activities, e.g., antifungal activity, antibacterial activity, cytotoxicity, antimalarial (Plasmodium falciparum) activity, inhibition of protein kinase C, and inhibition of IL-8 Rα and Rβ receptors. In the course of our study on the bioactive metabolites from marine organisms, we found that the ethanol extract of the ascidian Lissoclinum sp. (cf. L. badium Monniot, F. and Monniot, C., 1996) collected at Manado, Indonesia, showed strong antimicrobial activity against the fungus Mucor hiemalis and the marine bacterium Ruegeria atlantica. This ascidian does not have prochloron as a symbiont. Bioassay-guided separation gave three novel polysulfide aromatic alkaloids, named Iissoclibadins 1 (1), 2 (2), and 3 (3), together with a known dimeric polysulfide alkaloid, lissoclinotoxin F (4), and two known monomeric cyclic polysulfides 5 and 6. The structures of four known compounds were assigned on the basis of their spectral data and comparison with those of reported values. The gross structure of lissoclibadin 1 (1) was assigned on the basis of the spectral data as a trimeric polysulfide, and one of two possible isomers was selected by the computational modeling study. Lissoclibadin 1 inhibited the growth of R. atlantica (15.2 mm at 20 μg/disk). Two dimeric polysulfides lissoclibadins 2 (2) and 3 (3) were assigned the structures on the basis of their spectral data as trans-isomers of lissoclibadin F (4) and E, respectively. Compounds 1-6 showed different magnitudes of antimicrobial activity, and two monomeric compounds (5 and 6) had stronger and wider antimicrobial spectra among them. Lissoclibadin 3 (3) did not inhibit the growth of the five test microorganisms.
