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A screening program designed to find new antiinflammatory agents has identified the sponge meroterpenoid pelorol (1) as an in vitro activator of the inositol-5-phosphatase SHIP. Pelorol (1) and several functional group analogues have been synthesized from sclareolide (4).

Dominicin, a new cyclic peptide, and the new bromopyrrole alkaloid laughine (4) have been isolated from the marine sponge Eurypon laughlini collected in Dominica. The structures of 1 and 4 were determined by a combination of spectroscopic analysis and chemical degradation. Single-crystal X-ray diffraction analysis confirmed the structure of dominicin (1).

Investigation of the Indonesian sponge Acanthodendrilla sp. afforded five new luffariellolide-related sesterterpenes, acantholides A−E (1−5), in addition to luffariellolide and its 25-O-methyl and 25-O-ethyl derivatives. All structures were unambiguously established by 1D and 2D NMR and MS spectroscopy. Acantholide D and E are derivatives comprising the 1-acetylcyclopentan-5-ol moiety, which are new variants of the C14−C20 segment for this type of linear sesterterpenes. Luffariellolide and its 25-O-methyl congener as well as acantholide E (5) were cytotoxic against the mouse lymphoma L5187Y cell line. Acantholide B (2), luffariellolide, and its 25-O-methyl congener were active against the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, the Gram-negative bacterium Escherichia coli, the yeast Candida albicans, and the plant pathogenic fungus Cladosporium herbarum.

Chemical investigation of the sponge Leucetta chagosensis collected in Indonesia afforded five new imidazole alkaloids, naamine F (2), naamine G (3), kealiinine A (6), kealiinine B (7), and kealiinine C (8), in addition to the known compound naamine A (1). Naamine G (3) exhibited strong antifungal activity against the phytopathogenic fungus Cladosporium herbarum and also showed mild cytotoxicity against mouse lymphoma (L5178Y) and human cervix carcinoma (HeLa) cell lines. In the brine shrimp assay, kealiinine A (6) was more active than naamine G (3).The structures of the new compounds were unambiguously established by 1D and 2D NMR and MS data.

Two novel polyketides, spiculoic acids A (1) and B (2), have been isolated from extracts of the Caribbean marine sponge Plakortis angulospiculatus. The structures of 1 and 2 were elucidated by detailed analysis of spectroscopic data. Spiculoic acid A (1) showed in vitro cytotoxicity against human breast cancer MCF-7 cells. It has a putative polyketide biogenetic origin that involves incorporation of four butyrate units and a Diels Alderase catalyzed intramolecular [4 + 2] cycloaddition reaction.

Two novel antimitotic heterocyclic alkaloids, ceratamines A (1) and B (2), have been isolated from the marine sponge Pseudoceratina sp., collected in Papua New Guinea. The structures of 1 and 2 were elucidated by analysis of spectroscopic data.

Latonduines A (6) and B (7), two new alkaloids with unprecedented heterocyclic skeletons, have been isolated from the Indonesian marine sponge Stylissa carteri. The structures of the latonduines were elucidated by analysis of spectroscopic data and confirmed by the total synthesis of latonduine A (6). It is proposed that ornithine is the biogenetic precursor to the aminopyrimidine fragment of the latonduines.

Inhibitors of the G2 DNA damage checkpoint can selectively sensitize cancer cells with impaired p53 tumor suppressor activity to killing by DNA-damaging drugs or ionizing radiation and have been proposed as a promising therapeutic strategy. An extract from the Northeastern Pacific marine sponge Merriamum oxeato showed G2 checkpoint inhibitory activity, and fractionation identified the known dinoflagellate toxin dinophysistoxin 1 (1) and the two novel analogues 27-O-acetylokadaic acid (2) and 27-O-acetyldinophysistoxin 1 (3) as the active compounds. The mixture of 1, 2, and 3 was extremely potent at inhibiting the G2 checkpoint (IC50 = 1 ng/mL) and cellular protein Ser/Thr phosphatases (IC50 = 1 ng/mL), and it radiosensitized MCF-7 breast cancer cells expressing mutated p53 at all concentrations tested. However, the mixture of 1, 2, and 3 was also very toxic to cells not exposed to DNA damage (IC50 = 1 ng/mL), making these compounds poor candidates for therapeutic agents to augment the effectiveness of DNA-damaging therapies.

Thirteen new metabolites, melophlins C−O (1−13), were identified from the marine sponge Melophlus sarassinorum. Compounds 1−13 represent tetramic acid derivatives that differ with regard to the nature of their alkyl side chains. The structures of the new compounds were elucidated on the basis of comprehensive spectral analysis (¹H, ¹³C, ¹H−¹H COSY, HMQC, and HMBC NMR, as well as low- and high-resolution ESIMS and EIMS). The absolute configurations of 1, 8, 10, 11, 12, and 13 were determined by ESI LC/MS analysis of chiral derivatives obtained upon oxidation and hydrolysis of the respective parent compounds. Melophlin C (1) displayed pronounced antibacterial activity against Bacillus subtilis and Staphylococcus aureus, together with antifungal activity against Candida albicans.

Extracts of the marine sponge Caminus sphaeroconia showed potent activity in a screen for bacterial type III secretion inhibitors. Bioassay guided fractionation of the extract led to the isolation of the novel antimicrobial glycolipid caminoside A (1). The structure of caminoside A was elucidated by analysis of spectroscopic data and chemical degradation.

Analysis of the Papua New Guinean sponge Theonella swinhoei afforded a new calyculinamide-related congener for which we propose the name swinhoeiamide A (1). The structure of the new compound was unambiguously established on the basis of NMR spectroscopic (¹H, ¹³C, COSY, HMBC) and mass spectrometric (FABMS) data. Swinhoeiamide A exhibited insecticidal activity toward neonate larvae of the polyphagous pest insect Spodoptera littoralis when incorporated in an artificial diet offered to the larvae in a chronic feeding bioassay (ED50 2.11 ppm, LD50 2.98 ppm). Furthermore, it was found to be fungicidal against Candida albicans and Aspergillus fumigatus (MIC 1.2 and 1.0 μg/mL, respectively).

Glánvillic acids A (2) and B (3) and the cytotoxic cyclic peroxides methyl capucinoate A (4) and 5 were isolated from the Dominican marine sponges Plakortis halichondrioides and Plakinastrella onkodes, respectively. The structures have been elucidated by spectroscopic analysis of 4 and 5 and of methyl glánvillates A (6) and B (7).

Geodiamolides J−P (11−17) and R (19), eight new cyclic depsipetides, have been isolated from the marine sponge Cymbastela sp. collected in Papua New Guinea. The serine residue in geodiamolides L−P (13−17) and R (19) has not been previously found in this family of compounds.

(+)-Makassaric acid (1) and (+)-subersic acid (2), new meroterpenoid inhibitors of the protein kinase MK2, have been isolated from the marine sponge Acanthodendrilla sp. collected in Indonesia. The structures of (+)-makassaric acid (1) and (+)-subersic acid (2) were determined by spectroscopic analysis.

Three new sesquiterpenoids, boneratamides A (1)−C (3), have been isolated as their methyl esters 4−6 from extracts of the marine sponge Axinyssa aplysinoides collected in Indonesia. The structures of methyl esters 4−6 were elucidated by analysis of spectroscopic data and confirmed by single-crystal X-ray diffraction analysis of 4.

Strongylophorine-26 (1), a new meroditerpenoid that shows activity in an anti-invasion assay, has been isolated from the marine sponge Petrosia (Strongylophora) corticata collected in Papua New Guinea. The structure of 1 was elucidated by analysis of spectroscopic data.

The structure of trisphaerolide A (1), a mildly cytotoxic metabolite isolated from extracts of the marine sponge Erylus trisphaerus collected in Dominica, has been elucidated by detailed analysis of spectroscopic data. Trisphaerolide A (1) has a putative polyketide biogenesis, incorporating a rare variant on the standard pathway, which involves the addition of methyl branches arising from C-2 carbons of acetate units to chain carbons that arise from C-1 of acetate units.