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Research has been conducted on the pyridoacridine alkaloids, a class of marine-derived heteroaromatic pigments with cytotoxic activity. The study of the the deoxyamphimedine, a new pyridoacridine alkaloid, has been carried out in a purified enzyme system along with amphimedine and neoamphimedine and the results are discussed.

The pyridoacridines neoamphimedine and amphimedine were isolated from Xestospongia sp. from the Philippines and Xestospongia cf. carbonaria from Micronesia. The chemical formula, chemical shifts and proton coupling pattern for amphimedine is the same as for amphimedine isolated by Schmitz and colleagues. Neoamphimedine was found to be cytotoxic to normal CHO AAS cells. It was also observed that neoamphimedine stimulates topoisomerase II dependent cleavage 3% above controls compared to etoposide, which stimulates 38% cleavage at the same concentration.

Bolinaquinone, a sesquiterpene hydroxyquinone, was isolated and purified from the Philippine sponge Dysidea. The compound's molecular formula is C22H30O4. Bolinaquinone has a rearranged drimane skeleton and a different position for the hydroxyquinone moiety. It has been shown to be cytotoxic against a colon tumor cell line, against Bacillus subtilis and a Chinese hamster ovary cell line. The results of the characterization studies undertaken are presented.

The isolation of three new sulfated sterol dimers, fibrosterol sulfates A-C from the sponge Lissodendoryx (Acanthodoryx) fibrosa, collected in the Philippines is reported. The results offer insight into the structures assigned on the basis of extensive 1D and 2D NMR studies and the inhibition of PKC[zeta] with I[C.sub.50] values of 16.4 and 5.6 [mu]M, respectively.

The new linear peptides are cyclized via a cystine moiety and have their C-terminus blocked by a 2-phenylethylenamine group. The total structures including absolute stereochemistry, are determined by a combination of spectral and chemical methods.

Microbial isolate Z143-1 found to be associated with an unidentified tunicate was characterized due to its significant antimicrobial activity. Z143-1 is similar to Pseudovibrio ascidiaceicola and Pseudovibrio denitrificans in morphological, physiological and biochemical characteristics, except for its ability to ferment glucose and produce a characteristic red pigment. Fatty acid methyl ester analysis revealed a predominance of the fatty acid 18:1 ω7c at 80.55%, at levels slightly lower than the Pseudovibrio denitrificans type strain DN34T (87.7%). The mol% G+C of Z143-1 is 54.02, relatively higher than the Pseudovibrio denitrificans type strain DN34T and Pseudovibrio ascidiaceicola with mol% G+C of 51.7 and 51.4, respectively. However, phylogenetic analysis of the 16S rRNA gene sequence of Z143-1 showed 100% similarity with the Pseudovibrio denitrificans type strain DN34T. In this study, the bacterium Z143-1 is reported as a new strain of Pseudovibrio denitrificans. While there is no report of a secondary metabolite for Pseudovibrio denitrificans, Z143-1 produces the red pigment heptylprodigiosin, also known as 16-methyl-15-heptyl-prodiginine, which shows anti- Staphylococcus aureus activity. [ABSTRACT FROM AUTHOR]

Deals with a study which screened marine invertebrate extracts in a set of isogenic colorectal cancer cells as part of a search for biologically active natural products from marine organisms. Experimental details; Results and discussion; Conclusion.

Modulators of Wnt signaling have therapeutic potential in a number of human diseases. A fractionated library from marine invertebrates was screened in a luciferase assay designed to identify modulators of Wnt signaling. A fraction from a Carteriospongia sp. sponge activated Wnt signaling and was subsequently shown to inhibit GSK-3beta, which inhibits Wnt signaling through phosphorylation of beta-catenin. Three novel natural products, carteriosulfonic acids A (1), B (2), and C (3), were identified as active constituents. The carteriosulfonic acids contain unprecedented 4,6,7,9-tetrahydroxylated decanoic acid subunits. Their structures were elucidated through analysis of NMR data and a detailed analysis of pseudo MS(3) spectra.

Heptyl prodigiosin was purified from a culture of alpha-proteobacteria isolated from a marine tunicate collected in Zamboanga, Philippines, as part of a program to screen natural products for antiparasitic activity. An in vitro antimalarial activity similar to that of quinine was found against the chloroquine-sensitive strain Plasmodium falciparum 3D7. The in vitro antimalarial activity was about 20 times the in vitro cytotoxic activity against L5178Y mouse lymphocytes. A single subcutaneous administration of 5 and 20 mg/kg significantly extended survival of P. berghei ANKA strain-infected mice but also caused sclerotic lesions at the site of injection. A single administration by gavage of 50 mg/kg did not increase survival time. The compound was not found to be mutagenic using in vitro micromethods for the Ames Salmonella typhimurium assay and the micronucleus assay using L5178Y mouse lymphoma cells.

Raf/MEK-1/MAPK cascade inhibitor activity-directed fractionation of the sponge Stylissa massa afforded eight known alkaloids: aldisine (1), 2-bromoaldisine (2), 10Z-debromohymenialdisine (3), 10E-hymenialdisine (4), 10Z-hymenialdisine (5), hymenin (6), oroidin (7), and 4,5-dibromopyrrole-2-carbonamide (8). Both 4 and 5 showed significant enzyme inhibitory activity (IC(50) 3 and 6 nM, respectively). Secondary assays identified these compounds as potent MEK-1 inhibitors. Compounds 4 and 5 also inhibited the growth of human tumor LoVo cells.