Abstract
Malevamide D (1), a highly cytotoxic peptide ester, and the known compound curacin D (5) were isolated from a Hawaiian sample of Symploca hydnoides. The structure of 1 was elucidated by spectroscopic analysis including NMR and high-resolution MS/MS. Partial stereochemical assignments of 1 were made by chiral HPLC analysis of acid and base hydrolysates. Malevamide D (1) demonstrated toxicity against P-388, A-549, HT-29, and MEL-28 cell lines in the subnanomolar range, while curacin D (5) was weakly cytotoxic. Malevamide D (1) is closely related to isodolastatin H (2), which was previously isolated in low yield from the sea hare Dolabella auricularia. A second Hawaiian sample of S. hydnoides yielded curacin D (5) along with the known dolastatin-10 analogue symplostatin-1 (3).
Publication types
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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, Phytogenic / chemistry
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Antineoplastic Agents, Phytogenic / isolation & purification*
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Antineoplastic Agents, Phytogenic / pharmacology
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Chromatography, High Pressure Liquid
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Colonic Neoplasms
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Cyanobacteria / chemistry*
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Depsipeptides*
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Drug Screening Assays, Antitumor
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Hawaii
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Hydrolysis
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Inhibitory Concentration 50
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Leukemia P388
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Lung Neoplasms
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Melanoma
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Mice
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Molecular Structure
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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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Stereoisomerism
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Thiazoles / chemistry
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Thiazoles / isolation & purification
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Thiazoles / pharmacology
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Tumor Cells, Cultured / drug effects
Substances
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Antineoplastic Agents, Phytogenic
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Depsipeptides
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Oligopeptides
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Thiazoles
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isodolastatin H
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malevamide D
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symplostatin 1
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curacin D
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dolastatin 10