Compounds with antiviral, antineoplastic, immunomodulatory, antifungal, and antibacterial activities will be identified in marine species and their structures will be assigned. These include antineoplastic compounds from Ecteinascidia turbinata and new components of the didemnin (antiviral, antineoplastic, immunosuppressive) complex from Trididemnum solidum, as well as compounds from other tunicates, sponges, and algae. Bioassays to be employed in identifying active extracts and isolated compounds include tests against Herpes simplex virus, type I, Vesicular stomatitis virus, visna virus, and HIV-1; reverse transcriptase; cytotoxicity assays with L1210 murine leukemia and CV-1 monkey kidney cells; brine shrimp assay and Agrobacterium tumefaciens potato tumor assay; B-cell and T-cell mitogenesis inhibition, mixed lymphocyte reaction; and antimicrobial assays against Bacillus subtilis, Micrococcus luteus, Escherichia coli, Saccharomyces cerevisiae, and Penicillium atrovenetum. Compounds with antiviral, immunomodulatory, and cytotoxic activities will also be sought and identified in extensive collections of cyanobacteria (blue-green algae), insects, and plant species. Structures of the antifungal polyene antibiotics hamycin and aureofungin will also be studied. In addition, structural studies will be carried out on pretunichlorins, unique nickel-containing chlorins from T. solidum, on hepatotoxins from cyanobacteria, on iron-transport hydroxamates from Hemophilus influenzae, and on a hibernation- and fasting-characteristic compound produced by black bears and humans.
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