Candidaspongiolides, distinctive analogues of tedanolide from sponges of the genus Candidaspongia.
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.
Meragelman
Tamara L
TL
Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, Maryland, USA.
Willis
Richard H
RH
Woldemichael
Girma M
GM
Heaton
Andrew
A
Murphy
Peter T
PT
Snader
Kenneth M
KM
Newman
David J
DJ
van Soest
Rob
R
Boyd
Michael R
MR
Cardellina
John H
JH
McKee
Tawnya C
TC
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
D000970:Antineoplastic Agents; D007783:Lactones; D018942:Macrolides; C119775:tedanolide; D008049:Lipase