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

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.