| Marine organisms produce a vast array of secondary metabolites for chemical defense. Sponges collected from Hawaii, Jamaica, Micronesia, Indonesia, and the Red Sea were extracted and tested for activity against various diseases. Several known secondary metabolites were isolated by High Performance Liquid Chromatography (HPLC), elucidated and found to have bioactivity against tumor cell lines, microoganisms, malaria, HIV and bioluminescent marine bacteria.; Six of these marine natural products were used to generate nearly two hundred new semisynthetics by reacting readily available bioactive natural product scaffolds with commercially available small molecule libraries. The generation of molecular diversity, using the sophisticated structures of marine secondary metabolites, has yielded an exceptional number of active leads. Nine of the active compounds were scaled-up and their structures confirmed using Nuclear Magnetic Resonance (NMR) and High Resolution Mass Spectrometry (HRMS) experiments. The one-step semisynthesis makes this an attractive complimentary method for any high-throughput drug discovery program.; In addition, nineteen marine natural products were assayed for activity against the bioluminescent bacteria Vibrio fischeri to identify bioactive marine natural product leads. V. fischeri were exposed to purified marine natural products and activity was quantified by the measured decrease of emitted light. The observed decrease in light production after exposure of the sample indicates the presence of a toxin or biological activity. Several marine natural products were active against V. fischeri and their results tabulated and discussed. Being of marine origin, the bioluminescent bacteria may serve as a fast and relatively inexpensive method to detect bioactive marine natural products.; Finally, an antifreeze peptide from the Antarctic Sponge Homaxinella balfourensis was isolated and identified. Polar plants and animals survive in subzero waters (-2°C). Many of these marine organisms produce antifreeze proteins (AFPs) to better adapt themselves to these conditions. AFPs prevent ice crystals from destroying cell membranes by altering the crystallization and inhibiting the re-crystallization of water within the organism. The hydrophilic extract of the Antarctic sponge Homaxinella balfourensis exhibited a noncolligative freezing point depression effect on the crystal morphology of water. The extract was purified by HPLC, assayed, examined by NMR and appears to contain several AFPs. One peptide was isolated, analyzed by Matrix Assisted Laser Desorption Ionization (MALDI) mass spectrometry and the partial structure of the peptide identified through amino acid sequencing. These peptides have potential applications in agriculture, medicine and the food industry. |
