This proposal is to investigate microalgae, especially dinoflagellates, for novel antitumor, antiviral and antimicrobial agents. The research is also intended to determine if these microalgae are the primary sources of highly active interesting molecules recently discovered in marine invertebrates, and thus can be reliable sources of these potentially important therapeutic agents. Anticipated compounds include polyethers, macrolides, and other polyoxygenated compounds. The proposal is based on the recent findings of the occurrence of these compounds in dinoflagellates. Specifically, both free-living and symbiotic or associated organisms will be isolated and cultured in large scale. Emphasis will be on freshly isolated strains from natural habitats or hosts, although those held in culture collections and already in our possession will be also investigated. The cells and broths will be extracted, and the extracts will be fractionated guided by bioassays. The structures of purified compounds will be studied by physico-chemical methods including high field NMR, mass spectroscopy, and X-ray crystallography. Antitumor and antiviral assays will be conducted by Bristol-Myers Co., and NCI, and in- house cytotoxicity tests will be performed with limited cell lines as routine isolation guides. Antimicrobial tests will be done in house.
