Relationship between ionophoric and haemolytic activities of Perimycin (cas 11016-07-2) A and vacidin A, two polyene macrolide antifungal antibiotics

Add time:08/15/2019    Source:sciencedirect.com

The ionophoric and hemolytic activities of two antifungal aromatic heptaenes: vacidin A and Perimycin (cas 11016-07-2) 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.

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