Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1.
The potent antitumor agent dolastatin 10 (1) was originally isolated from the sea hare Dolabella auricularia, and we now report its isolation from the marine cyanobacterium Symploca sp. VP642 from Palau. The chemically related analogue symplostatin 1 (2) has been reisolated from Guamanian and Hawaiian varieties of S. hydnoides and its total stereochemistry completed by determining the N,N-dimethylisoleucine unit to be L. Symplostatin 1 (2), like dolastatin 10 (1), is a potent microtubule inhibitor. The antitumor activity of 2 was assessed in vivo against several murine tumors. Symplostatin 1 (2) was effective against a drug-insensitive mammary tumor and a drug-insensitive colon tumor; however, it was only slightly effective against two MDR tumors.
Luesch
H
H
Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA.
Moore
R E
RE
Paul
V J
VJ
Mooberry
S L
SL
Corbett
T H
TH
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001048:Aplysia / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000378:metabolism; D000458:Cyanobacteria / Q000737:chemistry* / Q000302:isolation & purification; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification; D047630:Depsipeptides; D018432:Drug Resistance, Multiple; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006141:Guam; D006254:Hawaii; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015674:Mammary Neoplasms, Animal / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D019029:Palau; D010190:Pancreatic Neoplasms / Q000378:metabolism; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D003603:Cytotoxins; D047630:Depsipeptides; D009842:Oligopeptides; C115534:symplostatin 1; C064570:dolastatin 10