DOI: 10.5176/978-981-08-8119-1_BioTech2011_9
Authors: Wanki Park, Soon-Chun Chung, So-Hyoung Lee, Jiyoung Park, Chan-Hong Ahn, Ki-Bong Oh
Abstract:
Oxazole-containing macrolides and structurally related marine metabolites are widely recognized to exhibit potent and diverse bioactivities such as antifungal activity, cytototoxicity, and icthyotoxicity as well as inhibition of cell division in fertilized sea urchin eggs. In continuation of our research for the discovery of inhibitors of enzymes from natural products, we encountered the marine sponge Chondrosia corticata, whose crude organic extract displayed significant cytotoxicity and antifungal activity. Bioassay-guided separation of the crude extracts using various chromatographic techniques yielded four oxazole-containing metabolites including halichondramide, jaspisamide A, and halishigamide D along with three new oxazole metabolites including neohalichondramide and (19Z)-halichondramide. The isolated compounds were evaluated for their in vitro activities toward isocitrate lyase (ICL) from Candida albicans, Na+/K+ ATPase from porcine cerebral cortex, and F-actin. These studies led to the identification of (19Z)-halichondramide as a potent actin depolymerization agent. The actin depolymerization activity by (19Z)-halichondramide was 4 times more potent than that of halichondramide. (19Z)-Halichondramide also have potent antifungal activity and inhibit ICL and Na+/K+ ATPase. The preliminary structure-activity relationship of these compounds is described to elucidate the essential structural requirements.
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