Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1977 Apr;11(4):615–618. doi: 10.1128/aac.11.4.615

Influence of Antioxidants on the Bioactivity of Amphotericin B

Fred A Andrews 1, William H Beggs 1, George A Sarosi 1
PMCID: PMC352038  PMID: 324396

Abstract

Four antioxidants, propyl gallate, butylated hydroxyanisole, butylated hydroxytoluene, and d-α-tocopherol acid succinate were found to stabilize amphotericin B and to prolong its antifungal activity against Candida albicans. Although each of the antioxidants was effective in this respect, propyl gallate and butylated hydroxyanisole were better than butylated hydroxytoluene and d-α-tocopherol acid succinate. None of the antioxidants alone adversely affected normal cell growth. It is suggested that amphotericin B instability is due, at least in part, to lability of the carbon-carbon double bonds of the polyene moiety toward autoxidation. By protecting the drug molecule with an antioxidant, it is possible to significantly lower the quantity of AB necessary to obtain particular antifungal effects.

Full text

PDF
618

Selected References

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

  1. Abernathy R. S. Treatment of systemic mycoses. Medicine (Baltimore) 1973 Sep;52(5):385–394. doi: 10.1097/00005792-197309000-00002. [DOI] [PubMed] [Google Scholar]
  2. Andrews F., Bjorksten J., Trenk F. B., Henick A. S., Koch R. B. The reaction of an autoxidized lipid with proteins. J Am Oil Chem Soc. 1965 Sep;42(9):779–781. doi: 10.1007/BF02631862. [DOI] [PubMed] [Google Scholar]
  3. Bonner D. P., Mechlinski W., Schaffner C. P. Stability studies with amphotericin B and amphotericin B methyl ester. J Antibiot (Tokyo) 1975 Feb;28(2):132–135. doi: 10.7164/antibiotics.28.132. [DOI] [PubMed] [Google Scholar]
  4. Branen A. L. Toxicology and biochemistry of butylated hydroxyanisole and butylated hydroxytoluene. J Am Oil Chem Soc. 1975 Feb;52(2):59–63. doi: 10.1007/BF02901825. [DOI] [PubMed] [Google Scholar]
  5. Cheung S. C., Medoff G., Schlessinger D., Kobayashi G. S. Stability of amphotericin B in fungal culture media. Antimicrob Agents Chemother. 1975 Oct;8(4):426–428. doi: 10.1128/aac.8.4.426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Di Luzio N. R. Antioxidants, lipid peroxidation and chemical-induced liver injury. Fed Proc. 1973 Aug;32(8):1875–1881. [PubMed] [Google Scholar]
  7. Fitch C. D. The red blood cell in the vitamin E-deficient monkey. Am J Clin Nutr. 1968 Jan;21(1):51–56. doi: 10.1093/ajcn/21.1.51. [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. Hamilton-Miller J. M. The effect of pH and of temperature on the stability and bioactivity of nystatin and amphotericin B. J Pharm Pharmacol. 1973 May;25(5):401–407. doi: 10.1111/j.2042-7158.1973.tb10035.x. [DOI] [PubMed] [Google Scholar]
  10. Lampen J. O. Amphotericin B and other polyenic antifungal antibiotics. Am J Clin Pathol. 1969 Aug;52(2):138–146. doi: 10.1093/ajcp/52.2.138. [DOI] [PubMed] [Google Scholar]
  11. Miller R. P., Bates J. H. Amphotericin B toxicity. A follow-up report of 53 patients. Ann Intern Med. 1969 Dec;71(6):1089–1095. doi: 10.7326/0003-4819-71-6-1089. [DOI] [PubMed] [Google Scholar]
  12. Oski F. A., Barness L. A. Hemolytic anemia in vitamin E deficiency. Am J Clin Nutr. 1968 Jan;21(1):45–50. doi: 10.1093/ajcn/21.1.45. [DOI] [PubMed] [Google Scholar]
  13. Rickards R. W., Smith R. M., Golding B. T. Macrolide antibiotic studies. XV. The autoxidation of the polyenes of the filipin complex and lagosin. Jpn J Antibiot. 1970 Dec;23(6):603–612. [PubMed] [Google Scholar]
  14. Shadomy S. In vitro studies with 5-fluorocytosine. Appl Microbiol. 1969 Jun;17(6):871–877. doi: 10.1128/am.17.6.871-877.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Tappel A. L. Lipid peroxidation damage to cell components. Fed Proc. 1973 Aug;32(8):1870–1874. [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES