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. 1979 May;15(5):716–722. doi: 10.1128/aac.15.5.716

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,†, K L Rinehart Jr 2
PMCID: PMC352743  PMID: 393163

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aszalos A. Differential potentiation by nystatin of the effect of antibiotics on yeast and mammalian cells. Antimicrob Agents Chemother. 1975 Jun;7(6):754–757. doi: 10.1128/aac.7.6.754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beezer A. E., Chowdhry B. Z., Newell R. D., Tyrrell H. J. Bioassay of antifungal antibiotics by flow microcalorimetry. Anal Chem. 1977 Oct;49(12):1781–1784. doi: 10.1021/ac50020a037. [DOI] [PubMed] [Google Scholar]
  3. Brandsberg J. W., French M. E. In vitro susceptibility of isolates of Aspergillus fumigatus and Sporothrix schenckii to amphotericin B. Antimicrob Agents Chemother. 1972 Nov;2(5):402–404. doi: 10.1128/aac.2.5.402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. CIRILLO V. P., HARSCH M., LAMPEN J. O. ACTION OF THE POLYENE ANTIBIOTICS FILIPIN, NYSTATIN AND N-ACETYLCANDIDIN ON THE YEAST CELL MEMBRANE. J Gen Microbiol. 1964 May;35:249–259. doi: 10.1099/00221287-35-2-249. [DOI] [PubMed] [Google Scholar]
  5. Cass A., Finkelstein A., Krespi V. The ion permeability induced in thin lipid membranes by the polyene antibiotics nystatin and amphotericin B. J Gen Physiol. 1970 Jul;56(1):100–124. doi: 10.1085/jgp.56.1.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gale E. F. The release of potassium ions from Candida albicans in the presence of polyene antibiotics. J Gen Microbiol. 1974 Feb;80(2):451–465. doi: 10.1099/00221287-80-2-451. [DOI] [PubMed] [Google Scholar]
  7. Gent M. P., Prestegard J. H. Interaction of the polyene antibiotics with lipid bilayer vesicles containing cholesterol. Biochim Biophys Acta. 1976 Feb 19;426(1):17–30. doi: 10.1016/0005-2736(76)90425-9. [DOI] [PubMed] [Google Scholar]
  8. Hamilton-Miller J. M. Chemistry and biology of the polyene macrolide antibiotics. Bacteriol Rev. 1973 Jun;37(2):166–196. [PMC free article] [PubMed] [Google Scholar]
  9. Hammarström L., Smith C. I. In vitro activating properties of polyene antibiotics for murine lymphocytes. Acta Pathol Microbiol Scand C. 1977 Aug;85C(4):277–283. doi: 10.1111/j.1699-0463.1977.tb03642.x. [DOI] [PubMed] [Google Scholar]
  10. Hammond S. M. Biological activity of polyene antibiotics. Prog Med Chem. 1977;14:105–179. doi: 10.1016/s0079-6468(08)70148-6. [DOI] [PubMed] [Google Scholar]
  11. Hammond S. M., Lambert P. A., Kliger B. N. The mode of action of polyene antibiotics; induced potassium leakage in Candida albicans. J Gen Microbiol. 1974 Apr;81(2):325–330. doi: 10.1099/00221287-81-2-325. [DOI] [PubMed] [Google Scholar]
  12. Kasumov Kh M., Liberman E. A. Ionnaia pronitsaemost' bimolekuliarnykh membran v prisutstvii polienovykh antibiotikov. I. Nistatin i amfoteritsin. Biofizika. 1972 Nov-Dec;17(6):1024–1031. [PubMed] [Google Scholar]
  13. Kasumov Kh M., Liberman E. A. Ionnaia pronitsaemost' bimolekuliarnykh membran v prisutstvii polienovykh antibiotikov. II. Levorin, trikhomitsin, kanditsidin. Biofizika. 1973 Mar-Apr;18(2):264–271. [PubMed] [Google Scholar]
  14. Kitajima Y., Sekiya T., Nozawa Y. Freeze-fracture ultrastructural alterations induced by filipin, pimaricin, nystatin and amphotericin B in the plasmia membranes of Epidermophyton, Saccharomyces and red complex-induced membrane lesions. Biochim Biophys Acta. 1976 Dec 2;455(2):452–465. doi: 10.1016/0005-2736(76)90317-5. [DOI] [PubMed] [Google Scholar]
  15. Kleinschmidt M. G., Chough K. S. Effect of filipin on liposomes prepared with different types of steroids. Plant Physiol. 1972 May;49(5):852–856. doi: 10.1104/pp.49.5.852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kotler-Brajtburg J., Medoff G., Schlessinger D., Kobayashi G. S. Amphotericin B and filipin effects on L and HeLa cells: dose response. Antimicrob Agents Chemother. 1977 May;11(5):803–808. doi: 10.1128/aac.11.5.803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kotler-Brajtburg J., Price H. D., Medoff G., Schlessinger D., Kobayashi G. S. Molecular basis for the selective toxicity of amphotericin B for yeast and filipin for animal cells. Antimicrob Agents Chemother. 1974 Apr;5(4):377–382. doi: 10.1128/aac.5.4.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lambert P. A., Hammond S. M. Potassium fluxes, first indications of membrane damage in micro-organisms. Biochem Biophys Res Commun. 1973 Sep 18;54(2):796–799. doi: 10.1016/0006-291x(73)91494-0. [DOI] [PubMed] [Google Scholar]
  19. Liras P., Lampen J. O. Sequence of candicidin action on yeast cells. Biochim Biophys Acta. 1974 Nov 4;372(1):141–153. doi: 10.1016/0304-4165(74)90081-6. [DOI] [PubMed] [Google Scholar]
  20. Little J. R., Plut E. J., Kotler-Brajtburg J., Medoff G., Kobayashi G. S. Relationship between the antibiotic and immunoadjuvant effects of amphotericin B methyl ester. Immunochemistry. 1978 Apr;15(4):219–224. doi: 10.1016/0161-5890(78)90058-5. [DOI] [PubMed] [Google Scholar]
  21. Medoff G., Kobayashi G. S. Amphotericin B. Old drug, new therapy.?2110. JAMA. 1975 May 12;232(6):619–620. doi: 10.1001/jama.232.6.619. [DOI] [PubMed] [Google Scholar]
  22. Norman A. W., Spielvogel A. M., Wong R. G. Polyene antibiotic - sterol interaction. Adv Lipid Res. 1976;14:127–170. [PubMed] [Google Scholar]
  23. Pandey R. C., Rinehart K. L., Jr Polyene antibiotics. IX. An improved method for the preparation of methyl esters of polyene antibiotics. J Antibiot (Tokyo) 1977 Feb;30(2):158–162. doi: 10.7164/antibiotics.30.158. [DOI] [PubMed] [Google Scholar]
  24. Pandey R. C., Rinehart K. L., Jr Polyene antibiotics. VII. Carbon-13 nuclear magnetic resonance evidence for cyclic hemiketals in the polyene antibiotics amphotericin B, nystatin A1, tetrin A, tetrin B, lucensomycin, and pimaricin1,2. J Antibiot (Tokyo) 1976 Oct;29(10):1035–1042. doi: 10.7164/antibiotics.29.1035. [DOI] [PubMed] [Google Scholar]
  25. Valeriote F., Lynch R., Medoff G., Kumar B. V. Protective effects of amphotericin B against spontaneous and transplantable murine tumors. J Natl Cancer Inst. 1976 Mar;56(3):557–560. doi: 10.1093/jnci/56.3.557. [DOI] [PubMed] [Google Scholar]
  26. Zygmunt W. A. Intracellular Loss of Potassium in Candida albicans After Exposure to Polyene Antifungal Antibiotics. Appl Microbiol. 1966 Nov;14(6):953–956. doi: 10.1128/am.14.6.953-956.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]

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