Two new brominated bis(indole) alkaloids, dragmacidins I (1) and J (2), showing low micromolar cytostatic activity, along with three known congeners were isolated from the Tanzanian sponge Dragmacidon sp. and their structures determined by the analysis of their NMR and MS data. From the study of their mechanism of action, it can be concluded that the mitotic arrest at metaphase in treated tumor cells, mediated by inhibition of PP1 and/or PP2A phosphatases is involved in the observed antiproliferative activity. Differences in their bioactivities were rationalized, and a plausible binding mode is proposed on the basis of computational simulations.
Two novel oxazole-thiazole containing cyclic hexapeptides, bistratamides M (1) and N (2) have been isolated from the marine ascidian Lissoclinum bistratum (L. bistratum) collected in Raja Ampat (Papua Bar, Indonesia). The planar structure of 1 and 2 was assigned on the basis of extensive 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration of the amino acid residues in 1 and 2 was determined by the application of the Marfey’s and advanced Marfey’s methods after ozonolysis followed by acid-catalyzed hydrolysis. The interaction between zinc (II) and the naturally known bistratamide K (3), a cyclic hexapeptide isolated from a different specimen of Lissoclinum bistratum, was monitored by 1H and 13C NMR. The results obtained are consistent with the proposal that these peptides are biosynthesized for binding to metal ions. Compounds 1 and 2 display moderate cytotoxicity against four human tumor cell lines with GI50 values in the micromolar range.
The previously reported 1-(2,4-dihydroxy-5-methylphenyl)ethan-1-one (1), (1’Z)-2-(1’,5’-dimethylhexa-1’,4’-dieny1)-5-methylbenzene-1,4-diol (2), and 1,8-epoxy-1(6),2,4,7,10-bisaborapentaen-4-ol (5) together with four new structures of aromatic bisabolane-related compounds (3, 4, 6, 7) were isolated from the marine sponge Myrmekioderma sp. Compounds 1, 2, and 5 were identified based on spectral data available in the literature. The structures of the four new compounds were experimentally established by 1D and 2D-NMR and (−)-HRESIMS spectral analysis. Cytotoxic and lipid-reducing activities of the isolated compounds were evaluated. None of the isolated compounds were active against the tested cancer cell lines; however, lipid-reducing activity was found for compounds 2–5 and 7 in the zebrafish Nile red fat metabolism assay. This class of compounds should be further explored for their suitability as possible agents for the treatment of lipid metabolic disorders and obesity.