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Open Access Publications from the University of California

The Natural Products Chemistry of Marine Ascidians: Structural Elucidation and Molecular Modeling Studies of Novel Secondary Metabolites


Ascidians are well-known producers of amino acid-derived secondary metabolites. Recent chemical and biological investigations of taxonomically diverse ascidians have revealed a variety of pharmacologically potent natural products and the importance of these metabolites in the survival of physically vulnerable ascidians in predator-rich habitats. However, at issue are the real sources of novel secondary metabolites isolated from marine ascidians, which are related to symbiosis due to complex associations of the ascidians with microbial symbionts. Furthermore, rapidly developing resistance of infectious diseases and cancers toward traditional antibiotics and anti-cancer drug needs unprecedented novel natural products. Despite great advance in separation science, marine natural products research in ascidians was relatively limited to nonpolar compounds. Furthermore, the aquatic environment implicates the significance of hydrophilic molecules in defensive adaptations and symbiosis. Therefore, the main objective of this research was to investigate biosynthetic diversity and limitation of ascidian secondary metabolism with emphasis of identification of hydrophilic bioactive molecules and unprecedented carbon skeletons. In this way, a broader understanding of ascidian secondary metabolism, and a chemical data base for studies of chemical ecology, could be established.

A variety of chromatographic methods, such as high performance liquid chromatography and high speed countercurrent chromatography, were used to isolate polar compounds. Extensive spectroscopic techniques, including a variety of two­ dimensional NMR experiments and mass spectrometric methods as well as computer­ molecular modeling, were utilized to elucidate their structures.

This research resulted in the structural elucidation of 25 new secondary metabolites in 10 different structural classes, including 8 new carbon skeletons from marine sources. A high diversity of chemical structures along with various bioactivities, such as cytotoxicity against colon cancer cells, antimicrobial activity, and anti inflammatory activity, were demonstrated. Several natural products showed cytotoxic activities directed against a drug-resistant human colon cell line, HCT 116. Some of these compounds are known to inhibit an enzyme which is frequently used as a chemotherapeutic target. In addition to them, some had antibacterial and antiinflammatory activities. However, not every compound was bioactive. Perhaps some of them may explain the chemical defense mechanism of marine ascidians against predators.

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