Membrane-permeabilizing activities of amphidinol 3, polyene-polyhydroxy antifungal from a marine dinoflagellate

Biochim Biophys Acta. 2004 Nov 17;1667(1):91-100. doi: 10.1016/j.bbamem.2004.09.002.


Amphidinols, which are polyene-polyhydroxy metabolites produced by the marine dinoflagellate Amphidinium klebsii, possess potent antifungal and hemolytic activities. The membrane permeabilizing actions of amphidinol 3, the most potent homologue, were compared with those of polyene antibiotics, amphotericin B (AmB) and filipin, in hemolytic tests, 23Na nuclear magnetic resonance (NMR)-based membrane permeabilizing assays, and UV spectroscopy for liposome-bound forms. In Na+ flux experiments using large unilamellar vesicles (LUVs), ion efflux by amphidinol 3 was inhibited by cholesterol or ergosterol, which was opposed to previous results [J. Mar. Biotechnol., 5 (1997) 124]. When the effect of the agents on the size of vesicles was examined by light scattering experiments, amphidinol 3 did not significantly alter their size while filipin and synthetic detergent Triton X-100 did. The observations implied that the activity of amphidinol 3 was mainly due to formation of large pores/lesions in liposomes rather than detergent-like disruption of membrane. The pore/lesion size was estimated to be 2.0-2.9 nm in diameter on the basis of osmotic protection experiments using blood cells. The UV spectra in liposomes, which revealed the close interaction of polyene moieties in a lipid bilayer, further implied that the membrane activity of amphidinol 3 is caused by the molecular assemblage formed in biomembrane. These results disclose that amphidinol 3 is one of few non-ionic compounds that possess potent membrane permeabilizing activity with non-detergent mechanism.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / pharmacology*
  • Amphotericin B / pharmacology
  • Animals
  • Antifungal Agents / pharmacology*
  • Cell Membrane Permeability / drug effects*
  • Cholesterol / pharmacology
  • Dinoflagellida / chemistry
  • Filipin / pharmacology
  • Hemolysis / drug effects
  • Liposomes
  • Nuclear Magnetic Resonance, Biomolecular
  • Porosity
  • Pyrans / pharmacology*
  • Sodium Isotopes / chemistry
  • Spectrum Analysis
  • Structure-Activity Relationship


  • Alkenes
  • Antifungal Agents
  • Liposomes
  • Pyrans
  • Sodium Isotopes
  • amphidinol 3
  • Amphotericin B
  • Filipin
  • Cholesterol