Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / isolation & purification*
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Antineoplastic Agents / pharmacology
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Chromatography, High Pressure Liquid
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Cyanobacteria / chemistry*
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Depsipeptides*
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Fibroblasts / drug effects
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Hawaii
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Humans
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Inhibitory Concentration 50
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KB Cells / drug effects
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Leukemia L1210
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Mass Spectrometry
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Mice
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Microscopy, Fluorescence
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Microtubules / drug effects
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Molecular Structure
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Neoplasms
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Nuclear Magnetic Resonance, Biomolecular
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Oligopeptides / chemistry
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Oligopeptides / isolation & purification*
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Oligopeptides / pharmacology
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Spectrometry, Mass, Electrospray Ionization
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Structure-Activity Relationship
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Thiazoles / chemistry
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Thiazoles / pharmacology
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Tumor Cells, Cultured / drug effects
Substances
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Antineoplastic Agents
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Depsipeptides
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Oligopeptides
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Thiazoles
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symplostatin 3
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dolastatin 1