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Polyphenols from two brown algae,Fucus vesiculosus (L.) andAscophyllum nodosum (L.) Le Jolis, inhibited feeding by the herbivorous snail,Littorina littorea. The active compounds were characterized as phloroglucinol polymers with a wide molecular weight range (mol wt <30,000 to >300,000) by spectroscopic, Ultrafiltration, thin-layer chromatographic, and chemical degradation data. As little as 1% (dry wt) polyphenol in food reduced feeding by more than 50%, and polyphenolic extracts inhibited feeding entirely when present in concentrations of 2-5% (dry wt). Commercially available phloroglucinol dihydrate and gallotannin, which are known herbivore feeding deterrents in terrestrial plants, inhibitedL. littorea feeding when added to food media in concentrations similar to those above. We conclude that polyphenols inF. vesiculosus andA. nodosum are functionally similar to terrestrial plant polyphenols (tannins) in providing chemical defenses against herbivores. This research is the first demonstration that chemical compounds defend these two dominant, perennial marine algae from the major herbivore found in their community.

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Twenty-four metabolites derived from marine sponges were evaluated for their cytotoxicities against two human tumor cell lines, non-small cell lung carcinoma A549 and colon adenocarcinoma HT-29, and against one murine leukemia cell line, P-388, and evaluated for their ability to effect signal transduction in a newly developed cell adhesion assay using an EL-4 cell line. The compounds included latrunculin A [1], batzelline A [2], chondrillin [3], aureol [4], epihippuristanol, theonellamine B, discorhabdins A and C, kabiramide C, dercitin, meridine, manzamines A, B, and C, 8,15-diisocyano-11(20)-amphilectene and the corresponding C-15 formamide, a 20-carbon acetylenic alcohol, 4,5-dihydro-6"-deoxybromotopsentin, epispongiadiol, isospongiadiol, puupehenone, reiswigin A, and demethyl- and demethyloxyaaptamine. Latrunculin A [1], batzelline A [2], chondrillin [3], and aureol [4] expressed the desired profile of a greater than five-fold level of cytotoxicity against A549 relative to P-388, and an effect in the cell adhesion assay. In this group of compounds, cytotoxicity toward A549 was equal to or more pronounced than against HT-29. Latrunculin A was evaluated in an sc-implanted human A549 lung tumor xenograft mouse model and yielded a T/C of 146%. Batzelline A was evaluated in the cancer cell line panel at the National Cancer Institute and found to express selective cytotoxicity against several melanoma cancer cell lines.

The application of Chiral Technology, or the (extensive) use of techniques or tools for the determination of absolute stereochemistry and the enantiomeric or chiral separation of racemic small molecule potential lead compounds, has been critical to successfully discovering and developing chiral drugs in the pharmaceutical industry. This has been due to the rapid increase over the past 10-15 years in potential drug candidates containing one or more asymmetric centers. Based on the experiences of one pharmaceutical company, a summary of the establishment of a Chiral Technology toolbox, including the implementation of known tools as well as the design, development, and implementation of new Chiral Technology tools, is provided.