title: Candidaspongiolides, distinctive analogues of tedanolide from sponges of the genus Candidaspongia.
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 components were 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.
authors.affiliation: Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, Maryland, USA.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Meragelman
authors.forename: Richard H
authors.initials: RH
authors.lastname: Willis
authors.forename: Girma M
authors.initials: GM
authors.lastname: Woldemichael
authors.forename: Andrew
authors.initials: A
authors.lastname: Heaton
authors.forename: Peter T
authors.initials: PT
authors.lastname: Murphy
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Snader
authors.forename: David J
authors.initials: DJ
authors.lastname: Newman
authors.forename: Rob
authors.initials: R
authors.lastname: van Soest
authors.forename: Michael R
authors.initials: MR
authors.lastname: Boyd
authors.forename: John H
authors.initials: JH
authors.lastname: Cardellina
authors.forename: Tawnya C
authors.initials: TC
authors.lastname: McKee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008049:Lipase / Q000378:metabolism; D018942:Macrolides; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry* / Q000145:classification; D013552:Swine
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; D018942:Macrolides; C119775:tedanolide; D008049:Lipase