Malevamide D: isolation and structure determination of an isodolastatin H analogue from the marine cyanobacterium Symploca hydnoides

J Nat Prod. 2002 Apr;65(4):487-91. doi: 10.1021/np010560r.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Chromatography, High Pressure Liquid
  • Colonic Neoplasms
  • Cyanobacteria / chemistry*
  • Depsipeptides*
  • Drug Screening Assays, Antitumor
  • Hawaii
  • Hydrolysis
  • Inhibitory Concentration 50
  • Leukemia P388
  • Lung Neoplasms
  • Melanoma
  • Mice
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Oligopeptides / chemistry*
  • Oligopeptides / isolation & purification*
  • Oligopeptides / pharmacology
  • Stereoisomerism
  • Thiazoles / chemistry
  • Thiazoles / isolation & purification
  • Thiazoles / pharmacology
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Depsipeptides
  • Oligopeptides
  • Thiazoles
  • isodolastatin H
  • malevamide D
  • symplostatin 1
  • curacin D
  • dolastatin 10