Isolation, structure determination, and biological activity of Lyngbyabellin A from the marine cyanobacterium lyngbya majuscula.
Lyngbyabellin A (1), a significantly cytotoxic compound with unusual structural features, was isolated from a Guamanian strain of the marine cyanobacterium Lyngbya majuscula. This novel peptolide is structurally related to dolabellin (2) in that both depsipeptides bear a dichlorinated beta-hydroxy acid and two functionalized thiazole carboxylic acid units. Its gross structure has been elucidated by spectral analysis, including 2D NMR techniques. The absolute stereochemistry of 1 was determined by chiral HPLC analysis of hydrolysis products and by characterization of the degradation products methyl 7,7-dichloro-3-hydroxy-2,2-dimethyloctanoate (3) and the corresponding acid 4. The total structure was further supported by molecular modeling studies. The isolation of 1 from L. majuscula once more supports the proposal that many compounds originally isolated from the sea hare Dolabella auricularia are of cyanobacterial origin. Lyngbyabellin A (1) was shown to be a potent disrupter of the cellular microfilament network.
Luesch
H
H
Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA.
Yoshida
W Y
WY
Moore
R E
RE
Paul
V J
VJ
Mooberry
S L
SL
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007624:KB Cells; D009682:Magnetic Resonance Spectroscopy; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C410925:lyngbyabellin A