Apratoxin E, a cytotoxic peptolide from a guamanian collection of the marine cyanobacterium Lyngbya bouillonii.
A collection of the marine cyanobacterium Lyngbya bouillonii from Guam afforded apratoxin E (1), a new peptide-polyketide hybrid of the apratoxin class of cytotoxins. The planar structure of 1 was elucidated by NMR spectroscopic analysis and mass spectrometry. Configurational assignments of stereocenters in the peptide portion were made by chiral HPLC analysis of the acid hydrolysate. The relative configuration in the polyketide moiety was assigned by comparison of NMR data including proton-proton coupling constants with those of the known analogues. Apratoxin E (1) displayed strong cytotoxicity against several cancer cell lines derived from colon, cervix, and bone, ranging from 21 to 72 nM, suggesting that the alpha,beta-unsaturation of the modified cysteine residue is not essential for apratoxin activity. The 5- to 15-fold reduced activity compared with apratoxin A (2) is attributed to the dehydration in the long-chain polyketide unit, which could affect the conformation of the molecule.
Matthew
Susan
S
Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, GainesVille, Florida 32610, USA.
Schupp
Peter J
PJ
Luesch
Hendrik
H
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000458:Cyanobacteria / Q000737:chemistry*; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006141:Guam; D006801:Humans; D008235:Lyngbya Toxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008387:Marine Toxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D009687:Nuclear Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
C438188:APTX protein, human; D000970:Antineoplastic Agents; D003603:Cytotoxins; D004268:DNA-Binding Proteins; D047630:Depsipeptides; D008235:Lyngbya Toxins; D008387:Marine Toxins; D009687:Nuclear Proteins; C442201:apratoxin A