Abstract

Classification of Polyene Antibiotics According to Chemical Structure and Biological Effects J. Kotler-Brajtburg 1 , G. Medoff 1 , G. S. Kobayashi 1 , S. Boggs 1 , D. Schlessinger 1 , R. C. Pandey 2 † and K. L. Rinehart Jr. 2 1 Washington University School of Medicine, St. Louis, Missouri 63110 2 University of Illinois, Urbana, Illinois 61801 ABSTRACT Fourteen polyene antibiotics and six of their semisynthetic derivatives were compared for their effects on potassium (K + ) leakage and lethality or hemolysis of either Saccharomyces cerevisiae or mouse erythrocytes. These polyene antibiotics fell into two groups. Group I antibiotics caused K + leakage and cell death or hemolysis at the same concentrations of added polyene. In this group fungistatic and fungicidal levels were indistinguishable. Group I drugs included one triene (trienin); tetraenes (pimaricin and etruscomycin); pentaenes (filipin and chainin); one hexaene (dermostatin); and one polyene antibiotic with unknown chemical structure (lymphosarcin). Group II antibiotics caused considerable K + leakage at low concentrations and cell death or hemolysis at high concentrations. The fungistatic levels were clearly separable from fungicidal. This group included the heptaenes (amphotericin B, candicidin, aureofungin A and B, hamycin A and B), and five of their semisynthetic derivatives (amphotericin B methyl ester, N -acetyl-amphotericin B, hamycin A and B methyl esters, and N -acetyl-candicidin). Nystatin, classified as a tetraene, and its derivative, N -acetyl nystatin, also were in this group.