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Research was conducted to examine adociasulfates 1-6, the inhibitors of kinesin motor proteins from the sponge Haliclona (aka Adocia) sp. The adociasulfates were isolated from an extract of the Palauan sponge Haliclona that inhibited the transport of stabilized microtubules by the motor protein kinesin that was immobilized on a microscope slide. Spectroscopic data determined the structures of adociasulfates 1-6, the relative stereochemistry of adociasulfates 1,2,5 and 6 and the relative stereochemistry of subunits of adociasulfates 3 and 4.

Symbiotic filamentous bacteria of the sponge Theonella swinhoei contain a major bicyclic peptide called theopalauamide. Proton nuclear magnetic resonance studies, gas chromatographic analysis and mass spectrometry were undertaken to determine its stereochemistry. The analysis of the degradation products of theopalauamide by chiral GC-MS helped in establishing the stereochemical characteristics of this compound.

The isolation and characterization of four new alkaloids, batzelladines F-I, from the sponge Batzellia sp. are described. The compounds were isolated by a bioassay-directed fractionation technique. The alkaloids have been found to induce dissociation of the p56llkc-CDK complex at micromolar concentrations.

The three cyclic peptides, aciculitins A-C, from the lithistid sponge Aciculites orientalis are homologous but differ in the length of the alkyl chain. Aciculitins A-C are cytotoxic to the human-colon tumor cell line HCT-116 and limits the growth of Candida albicans. The characteristics histidine-tyrosine bridge is present in the bicyclic peptide of the aciculitins. The C13-C15 2,3-dihydroxy-4,6-dienoic acids containing D-lyxose are bonded to the 3-position of the bicyclic peptide.

An ELISA-based assay reveals that two guanidine alkaloids, batzelladines A and B, of the Caribbean sponge Batzella sp. inhibit the HIV gp120-human CD4 binding. Extraction procedures enable the separation of five novel alkaloids, batzelladines A to E. Spectral analysis and chemical degradation studies help determine the structures of these alkaloids.

Spectroscopic analysis of theonegramide, an antifungal glycopeptide from the Philippine lithistid sponge Theonella swinhoei, shows that it contains an arabinose connected to a bicyclic dodecapeptide having unusual amino acids, and histidinoalanine. A comparative study between the structures of theongramide and theonellamide reveals similarities but four of the 12 amino acid residues are different. GC-MS analysis determines the absolute configuration of theonegramide using a chiral column packing.

Spectroscopic studies help characterize the structure of microsclerodermins, which are cyclic hexapeptides isolated from the lithistid sponge Microscleroderma. NMR, NOE results and GC-MS analyses of the degradation products help assign the absolute stereochemistry of 10 asymmetric centers in the microsclerodermins. Transmission electron microscopic studies show that these filamentous microorganisms are members of the family Beggiatoaceae.

A new type of polychlorinated amino acid obtained from Dysidea herbacea was separated and its structure was examined. 10-Dechlorodysideathiazole, 9,10-didechloro-N-methyldysideathiazole and 10-dechloro-N-methyldysideathiazole were separated from a Palauan specimen. The pattern of dysideathiazole-dysideapyrrolidone was described using spectroscopic techniques.

The sponge Leucetta microraphis yields two antimicrobial lipids, leucettamols A and B, as active components of the pteridine alkaloid leucettidine. Spectroscopic analysis reveals the two as hexaenic conjugated polyols, possessing the characteristic optical inactivity of the leucettamols. Leucettamol A is assigned the molecular formula C30H52N2O2 and Leucettamol B, C30H52N2O3. Leucettamol B, a triol has one more secondary hydroxyl than A. The two are only mildly active against B. subtilis.

The mechanism involved in the inactivation of bee venom phospholipase A2 (PLA2) by manoalide, luffariellolide and scalaradial was investigated. Model reactions indicated imine formation between the hemiacetal or aldehyde functionalities in the inhibitors and lysine residues in PLA2 as the major reaction involved. Results also provide evidence for the further reaction of scalaradial to form a pyrrole adduct. Likewise, luffariellolide reacts with lysine to yield a gamma-(alkylamino)butenolide and manoalide reactsto give a gamma-(alkylamino)butenolide then a drug-enzyme adduct.

Spectral analysis of the compounds isolated from the Axinyssa aplysinoides marine sponge from Palau showed that the metabolites contained the thiocyanate (1R*,2R*,3R*,5R*,6S*,7S*)-2-thiocyanatopupukeanane. Moreover, two other specimens from Pohnpei, Caroline Islands, were examined using infrared and C NMR analyses. The first was found to contain the isothiocyanates, (1S*,2R*,5S*,6S*,7R*,8S*)-13-isothiocyanatocubebane and (1R*, 4S*,5R*,6S*,7S*,10R*)-1-isothiocyanatoaromadendrane, while the second was found to contain an axisonitrile-3 and a sesquiterpene thiocycanate with an unusual stereochemistry at C2.

X-ray studies of stellettamine, along with spectroscopic and metal-binding studies of the kuanoniamine D, prompt the revision of structures earlier reported for four related alkaloids. The structure of the thiazole moiety of dercitin, cyclodercitin, nordercitin, dercitamide and dercitamine was incorrectly reported for lack of a proper correlation technique at that time. The isolation and characterization of the kuanoniamines, where the thiazole structure is reversed, encouraged a reinvestigation of the dercitins. Apart from leading to structural revision, the new probe reveals that dercitamide and kuanoniamine C are one and the same.

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.

The large-scale isolation of manoalide from Luffariella variabilis yields secondary metabolites including (4E,6E)-dehydromanoalide and luffalactone, a tetracyclic sesterterpene acetate. The monoalide is a potent antiinflammatory agent and phospholipase A2 inhibitor. The metabolites are characterized following their coelution with dehydromanoalide during column chromatography. The bioactivity of (4E, 6E)-dehydromanoalide is already known while luffalactone, based on bioassays, is shown to exhibit 52% inhibition potency against edema.

The marine sponge Leucetta microrhaphis yields a new imidazole alkaloid along with the known clathridine zinc complex. The new metabolite, (9E)-clathridine 9-N-(2-sulfoethyl)imine, crystallizes as a yellow needle with a melting point of 275-277 degrees C. High-resolution mass measurement sets its molecular formula as C18H20N6O6S. Spectroscopic studies suggest a 1,3,4-trisubstituted benzene ring, with a methyleneoxy ring occupying the C-3 and C-4 positions. The major difference with the zinc complex is a two-carbon unit attached to ring A. An X-ray study also reveals a taurine residue at C-9 that hinders complexation with zinc.

Koshikamide B is isolated from two separate collections of the marine sponge Theonella sp. Its structure is determined by interpretation of spectral data and analysis of chemical degradation products.