Malevamide D: isolation and structure determination of an isodolastatin H analogue from the marine cyanobacterium Symploca hydnoides.
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).
Horgen
F David
FD
Natural Sciences, Hawaii Pacific University, Kaneohe, Hawaii 96744, USA.
Kazmierski
Emily B
EB
Westenburg
Hans E
HE
Yoshida
Wesley Y
WY
Scheuer
Paul J
PJ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides; D004354:Drug Screening Assays, Antitumor; D006254:Hawaii; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D007941:Leukemia P388; D008175:Lung Neoplasms; D008545:Melanoma; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D013237:Stereoisomerism; D013844:Thiazoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D047630:Depsipeptides; D009842:Oligopeptides; D013844:Thiazoles; C455547:isodolastatin H; C455546:malevamide D; C115534:symplostatin 1; C116945:curacin D; C064570:dolastatin 10