Studies on the biological properties of polyene antibiotics: Comparison of other polyenes with filipin in their ability to interact specifically with sterol

Abstract

1.1. The interaction fo the five polyene antibiotics filipin, etruscomycin, pimaricin, nystatin and amphotericin B with sterol, primarily free, liposomal and membrane bound cholesterol has been examined. Each of these antibiotics has a characteristic ultraviolet absorption spectrum in aqueous or organic solvents with three or four ultraviolet absorption maxima.Addition of free cholesterol to aqueous solutions of these antibiotics results in a change of the ratio of the ultraviolet absorbance maxima. The order of effectiveness of interaction with cholesterol as judged by this criterion was filipin, amphotericin B, etruscomycin and pimaricin. 2. 2. The same alteration in ultraviolet absorption spectra of filipin etruscomycin and amphotericin B observed with addition of free cholesterol to aqueous solutions of these antibiotics also occurs upon addition of these antibiotics to liposomal, erythrocyte or Acholeplasma membrane bound cholesterol. No spectral change was found in membranes devoid of cholesterol. This spectra alteration of the antibiotic was accompanied by a binding of the antibiotic to the membrane. Both nystatin and pimaricin showed little change in spectrum with sterol in these systems, either the artificial or natural membranes which contained cholesterol. 3. 3. The structural requirements of the sterol for the spectral change with filipin, etruscomycin and amphotericin B include a planar sterol nucleus, and intact side chain at C-17 and 3β-hydroxyl group. The spectral change was not affected by the pH except in the case of amphotericin B. 4. 4. Measurements by differential scanning calorimetry of the effect of these polyene antibiotics on the phase transition of lecithin and lecithin-cholesterol showed that all polyenes can reduce the ecithin cholesterol interaction.