1. Candidaspongiolides, Distinctive Analogues of Tedanolide from Sponges of the Genus Candidaspongia
- Author
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J.H. Cardellina, David J. Newman, Andrew Heaton, Tawnya C. McKee, Peter T. Murphy, Richard H. Willis, Rob van Soest, Girma M. Woldemichael, Kenneth M. Snader, Tamara L. Meragelman, Michael R. Boyd, and Research of the Zoological Museum of Amsterdam (ZMA)
- Subjects
Swine ,Stereochemistry ,Chemical structure ,Triacylglycerol lipase ,Pharmaceutical Science ,Antineoplastic Agents ,Fractionation ,Biology ,Article ,Analytical Chemistry ,Lactones ,Drug Discovery ,Animals ,Humans ,Organic chemistry ,Lipase ,Nuclear Magnetic Resonance, Biomolecular ,Pharmacology ,chemistry.chemical_classification ,Molecular Structure ,Organic Chemistry ,Fatty acid ,Biological activity ,biology.organism_classification ,Porifera ,Sponge ,Complementary and alternative medicine ,chemistry ,biology.protein ,Molecular Medicine ,Macrolides ,Drug Screening Assays, Antitumor ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Fractionation of cytotoxic extracts of specimens of a newly described sponge genus, Candidaspongia, has yielded the candidaspongiolides (3), a complex mixture of acyl esters of a macrolide related to tedanolide. The general structure of the candidaspongiolides was determined by analyses of various 2D NMR and MS data sets. The acyl ester componentswere identified by GC-MS analysis of the derived fatty acid methyl esters. The mixture could be selectively converted to the deacylated macrolide core (4) by enzymolysis with immobilized porcine lipase, with the structure of the candidaspongiolide core then secured by NMR and MS analysis. The candidaspongiolide mixture was potently cytotoxic, exhibiting a mean panel 50% growth inhibition (GI50) of 14 ng/mL in the National Cancer Institute’s 60-cell-line in Vitro antitumor screen.
- Published
- 2007