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Extracts of samples of a Caribbean tunicate (ascidian, sea squirt) of the family Didemnidae inhibit in vitro at low concentrations the growth of DNA and RNA viruses as well as L1210 leukemic cells. The active compounds isolated from the tunicate, didemnins A, B, and C, are depsipeptides, and didemnin B (a derivative of didemnin A) is the component active at the lowest concentration in inhibiting viral replication in vitro and P388 leukemia in vivo.

Water blooms formed by potentially toxic species of cyanobacteria are a common phenomenon in the Baltic Sea in late summer. Twenty-five cyanobacterial bloom samples were collected from open and coastal waters of the Baltic Sea during 1985 to 1987, and their toxicity was determined by mouse bioassay. All of 5 bloom samples from the southern Baltic Sea, 6 of 6 from the open northern Baltic Sea (Gulf of Finland), and 7 of 14 Finnish coastal samples were found to contain hepatotoxic cyanobacteria. Nodularia spumigena and Aphanizomenon flos-aquae occurred together in high amounts in blooms from the open-sea areas. In addition, coastal samples contained the species Anabaena lemmermannii, Microcystis aeruginosa, and Oscillatoria agardhii. Eighteen hepatotoxic N. spumigena cultures were isolated from water bloom and open-sea water samples. High-pressure liquid chromatographic analysis of both hepatotoxic bloom samples and Nodularia strains showed a single toxic fraction. The toxin concentrations of the blooms were .2.4 mg/g of freeze-dried material, and those of laboratory-grown cultures were 2.5 to 8.0 mg/g of freeze-dried cells. A single toxin was isolated from three N. spumigena-containing bloom samples and three N. spumigena laboratory isolates. Amino acid analysis and lowand high-resolution fast-atom bombardment mass spectroscopy indicated that the toxin from all of the sources was a cyclic pentapeptide (molecular weight, 824) containing glutamic acid, I-methylaspartic acid, arginine, N-methyldehydrobutyrine, and 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid. This indicates that the Baltic Sea toxin is nodularin, the cyclic pentapeptide produced by field and laboratory-cultured N. spumigena previously reported from New Zealand brackish water lakes. The signs of poisoning by the pentapeptide were similar to those reported for the heptapeptide toxins from other cyanobacteria.

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† " This paper is dedicated to the memory of P J. Scheuer (1916Scheuer ( -2003 Abstract: Nature has been instrumental as a source for therapeutics. Despite the fact that we live in an oceanic planet, a number of technical factors have historically hampered the evolution of a marine-based chamanic medicine. With the implementation of scuba diving tools and the development of sophisticated instruments for the isolation and elucidation of structures of natural products from Mar. Drugs 2004, 2 15 marine organisms, major advances have been made in the discovery of marine derived therapeutics. The availability of ARA-C, a nucleoside analog that is a basic component in the treatment of acute myeloid leukemia, and its fluorinated analog Gemcitabine, an important therapeutic tool in the treatment of pancreatic cancer and in non small cell lung cancer, is a solid proof and validation of the potential of this approach. As a result of our discovery and developmental program, three innovative compounds with novel mechanisms of action: ET-743, Aplidin R and Kahalalide F, have been shown to display a positive therapeutic index and activity in resistant solid tumors that supports the ongoing clinical phase III/II trials. ET-743 represents the first active agent against sarcomas developed in the past 25 years and has demonstrated a therapeutic potential in pretreated ovarian cancer. Several chemical entities are under advanced preclinical testing and additional candidates for clinical development are emerging, including compounds hitting a specific target. Moreover, the development of a given marine candidate implies the collaboration of an interdisciplinary team special focused on supply, formulation, pharmacogenetics and preclinical toxicology.