Further studies on the hemolytic action of filipin and derivatives

The interaction of filipin with model membrane systems, such as lipid monomolecular layers and bilayer films, has been described previously. To find additional criteria by which to evaluate various membrane models, several methods for producing derivatives of filipin, which have little or no biological activity, have been examined. Two methods have proved particularly useful: (a) reduction of the conjugated double bond sequence and (b) irradiation with visible light in the presence of FMN. Perhydrofilipin has approx. 1/100 the hemolytic activity of the parent antibiotic, whereas irradiated filipin no biological activity (either hemolytic or antifungal). The effect of these derivatives on model membrane systems is described in the following papers. We have extended our observations that also the antibiotic/erythrocyte ratio, and not only the absolute concentration of antibiotic, determines the rate and extent of hemolysis. This finding provides an additional criterion which must be met by an appropriate membrane model