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.
Cybulska
B
B
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdansk, Poland.
Borowski
E
E
Gary-Bobo
C M
CM
D000098:Acetophenones / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D002174:Candicidin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004911:Erythrocyte Volume / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007476:Ionophores; D011188:Potassium / Q000097:blood; D013997:Time Factors
D000098:Acetophenones; D000935:Antifungal Agents; D007476:Ionophores; D002174:Candicidin; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; C031985:vacidin A; C001266:fungimycin; D011188:Potassium