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. 1988 Mar;32(3):327–330. doi: 10.1128/aac.32.3.327

Interference with effects of amphotericin B on Candida albicans cells by 2-chloroethyl-1-nitrosoureas.

J Brajtburg 1, S Elberg 1, G S Kobayashi 1, G Medoff 1
PMCID: PMC172169  PMID: 3284460

Abstract

Two nitrosoureas, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), with strong carbamoylating and weak alkylating activities, interfered with the induction of potassium leakage and lethal action of amphotericin B (AmB) on Candida albicans. 2-Cyclohexyl isocyanate, the product of decomposition of CCNU, and 2-chloroethyl isocyanate, the product of decomposition of BCNU, also interfered with the anticandidal actions of AmB. In contrast, two nitrosoureas with weak carbamoylating and strong alkylating activities, 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperydyl)-1-nitrosourea and 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose, did not affect AmB action against C. albicans. These results indicate that the inhibitory action of CCNU and BCNU on the anticandidal effects of AmB is associated with the carbamoylating activity of these nitrosoureas.

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Selected References

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

  1. Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121–126. doi: 10.1016/s0076-6879(84)05016-3. [DOI] [PubMed] [Google Scholar]
  2. Brajtburg J., Elberg S., Schwartz D. R., Vertut-Croquin A., Schlessinger D., Kobayashi G. S., Medoff G. Involvement of oxidative damage in erythrocyte lysis induced by amphotericin B. Antimicrob Agents Chemother. 1985 Feb;27(2):172–176. doi: 10.1128/aac.27.2.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brajtburg J., Kobayashi D., Medoff G., Kobayashi G. S. Antifungal action of amphotericin B in combination with other polyene or imidazole antibiotics. J Infect Dis. 1982 Aug;146(2):138–146. doi: 10.1093/infdis/146.2.138. [DOI] [PubMed] [Google Scholar]
  4. Gale E. F. Nature and development of phenotypic resistance to amphotericin B in Candida albicans. Adv Microb Physiol. 1986;27:277–320. doi: 10.1016/s0065-2911(08)60307-0. [DOI] [PubMed] [Google Scholar]
  5. Kann H. E., Jr, Schott M. A., Petkas A. Effects of structure and chemical activity on the ability of nitrosoureas to inhibit DNA repair. Cancer Res. 1980 Jan;40(1):50–55. [PubMed] [Google Scholar]
  6. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  7. Levin V. A., Hoffman W., Weinkam R. J. Pharmacokinetics of BCNU in man: a preliminary study of 20 patients. Cancer Treat Rep. 1978 Sep;62(9):1305–1312. [PubMed] [Google Scholar]
  8. Oliverio V. T., Vietzke W. M., Williams M. K., Adamson R. H. The absorption, distribution, excretion, and biotransformation of the carcinostatic 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in animals. Cancer Res. 1970 May;30(5):1330–1337. [PubMed] [Google Scholar]
  9. Sokol-Anderson M. L., Brajtburg J., Medoff G. Amphotericin B-induced oxidative damage and killing of Candida albicans. J Infect Dis. 1986 Jul;154(1):76–83. doi: 10.1093/infdis/154.1.76. [DOI] [PubMed] [Google Scholar]
  10. Vertut-Croquin A., Brajtburg J., Medoff G. Two mechanisms of synergism when amphotericin B is used in combination with actinomycin D or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea against the human promyelocytic leukemia cell line HL-60. Cancer Res. 1986 Dec;46(12 Pt 1):6054–6058. [PubMed] [Google Scholar]
  11. Wheeler G. P., Bowdon B. J., Grimsley J. A., Lloyd H. H. Interrelationships of some chemical, physicochemical, and biological activities of several 1-(2-haloethyl)-1-nitrosoureas. Cancer Res. 1974 Jan;34(1):194–200. [PubMed] [Google Scholar]

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