Relationship between ionophoric and haemolytic activities of perimycin A and vacidin A, two polyene macrolide antifungal antibiotics

Abstract The ionophoric and hemolytic activities of two antifungal aromatic heptaenes: vacidin A and perimycin A, were studied on human red blood cells. Measurements of hemolysis, K + influx and efflux, H + movement and potential difference across the cell membrane, show that the hemolytic activity, being related to the K + permeability induced by the polyene, is strongly dependent on the ability of this polyene to induce H + movement. It was shown that: (1) both antibiotics have approximately the same efficiency in inducing K + permeability, but a 100-fold difference in their hemolytic activity; (2) their hemolytic activity is related to their ability to induce H + movement; (3) the protonophoric activity requires the existence of a free carboxyl group in the macrolide ring, as in vacidin A. The hemolytic activity is determined by the intrinsic efficiency of a K + /H + exchange induced by this polyene. With perimycin A, which lacks the free carboxyl group, the hemolytic activity is dependent on the Cl + conductive flux which slows down the K + flux.