Isolation, structure determination, and biological activity of dolastatin 12 and lyngbyastatin 1 from Lyngbya majuscula/Schizothrix calcicola cyanobacterial assemblages.
Lyngbyastatin 1 (1a), a new cytotoxic analogue of dolastatins 12 (2a) and 11 (4), was isolated as an inseparable mixture with its C-15 epimer (1b) from extracts of a Lyngbya majuscula/Schizothrix calcicola assemblage and a L. majuscula strain collected near Guam. Dolastatin 12 (2a) was also encountered as an inseparable mixture with its C-15 epimer (2b) in L. majuscula/S. calcicola assemblages. At least one of the compounds in each mixture appeared to exist in solution as a mixture of slowly interconverting conformers resulting in broadened signals in 1H NMR spectra. Structure elucidation therefore relied principally on mass spectroscopy and chemical degradation studies. Both 1ab and 2ab proved toxic with only marginal or no antitumor activity when tested against colon adenocarcinoma #38 or mammary adenocarcinoma #16/C. Both 1ab and 2ab were shown to be potent disrupters of cellular microfilament networks.
Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822.
G G
GG
Harrigan
W Y
WY
Yoshida
R E
RE
Moore
D G
DG
Nagle
P U
PU
Park
J
J
Biggs
V J
VJ
Paul
S L
SL
Mooberry
T H
TH
Corbett
F A
FA
Valeriote
D008841:Actin Cytoskeleton / Q000187:drug effects; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002460:Cell Line; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides; D004354:Drug Screening Assays, Antitumor; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D000970:Antineoplastic Agents; D047630:Depsipeptides; D009842:Oligopeptides; C115556:dolastatin 12; C115557:lyngbyastatin 1