Classification of Polyene Antibiotics According to Chemical Structure and Biological Effects

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.