Five new discodermolide analogues from the marine sponge Discodermia species.
Discodermolide (1) and five new discodermolide analogues trivially named 2-epi-discodermolide (2), 2-des-methyldiscodermolide (3), 5-hydroxymethyldiscodermolate (4), 19-des-aminocarbonyldiscodermolide (5), and 9(13)-cyclodiscodermolide (6) have been isolated from marine sponges belonging to the genus Discodermia collected from the Caribbean Sea. The isolation, structure elucidation, and biological activities of 2-6 are described. The natural analogues, which were isolated in trace amounts, exhibited significant variation of cytotoxicity against the cultured murine P-388 leukemia and A-549 human adenocarcinoma cells and suggested the importance of the C(7) through C(17) moiety for potency against cultured tumor cell lines.
Gunasekera
Sarath P
SP
Division of Biomedical Marine Research, Harbor Branch Oceanographic Institution, 5600 US 1 North, Fort Pierce, Florida 34946, USA. sgunaseker@hboi.edu
Paul
Gopal K
GK
Longley
Ross E
RE
Isbrucker
Richard A
RA
Pomponi
Shirley A
SA
D000230:Adenocarcinoma; D000818:Animals; D017691:Caribbean Region; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007941:Leukemia P388; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007783:Lactones; C471525:discodernolide