Symplostatin 3, a new dolastatin 10 analogue from the marine cyanobacterium Symploca sp. VP452.
Symplostatin 3 (1), a new analogue of dolastatin 10 (2), has been isolated from a tumor selective extract of a Hawaiian variety of the marine cyanobacterium Symploca sp. VP452. Compound 1 differs from 2 only in the C-terminal unit; the dolaphenine unit is substituted by a 3-phenyllactic acid residue. Symplostatin 3 (1) possesses IC(50) values for in vitro cytotoxicity toward human tumor cell lines ranging from 3.9 to 10.3 nM. It disrupts microtubules, but at a higher concentration than 2, correlating with the weaker in vitro cytotoxicity.
Luesch
Hendrik
H
Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA.
Yoshida
Wesley Y
WY
Moore
Richard E
RE
Paul
Valerie J
VJ
Mooberry
Susan L
SL
Corbett
Thomas H
TH
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects; D006254:Hawaii; D006801:Humans; D020128:Inhibitory Concentration 50; D007624:KB Cells / Q000187:drug effects; D007939:Leukemia L1210; D013058:Mass Spectrometry; D051379:Mice; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects; D015394:Molecular Structure; D009369:Neoplasms; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D047630:Depsipeptides; D009842:Oligopeptides; D013844:Thiazoles; C449919:symplostatin 3; C032227:dolastatin 1