Abstract
Ketoconazole, an orally active antimycotic drug, is a potent inhibitor of ergosterol biosynthesis in Candida albicans when added to culture media which support yeast or mycelial growth or to cultures containing outgrown mycelium. This inhibition coincides with accumulation of sterols with a methyl group at C-14 and can thus be attributed to an interference with one of the reactions involved in the removal of the 14 alpha-methyl group of lanosterol. When administered to rats infected with C. albicans, ketocanazole also inhibits fungal synthesis of ergosterol. A six-times-higher dose is required to effect cholesterol synthesis by rat liver.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bisschop M. P., Merkus J. M., Scheygrond H., Van Cutsem J., van de Kuy A. Treatment of vaginal candidiasis with ketoconazole, a new, orally active, antimycotic. Eur J Obstet Gynecol Reprod Biol. 1979 Aug;9(4):253–259. doi: 10.1016/0028-2243(79)90065-0. [DOI] [PubMed] [Google Scholar]
- Bloch K. E. Speculations on the evolution of sterol structure and function. CRC Crit Rev Biochem. 1979 Nov;7(1):1–5. doi: 10.3109/10409237909102566. [DOI] [PubMed] [Google Scholar]
- Borgers M., De Brabander M., Van Den Bossche H., Van Cutsem J. Promotion of pseudomycelium formation of Candida albicans in culture: a morphological study of the effects of miconazole and ketoconazole. Postgrad Med J. 1979 Sep;55(647):687–691. doi: 10.1136/pgmj.55.647.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Botter A. A., Dethier F., Mertens R. L., Morias J., Peremans W. Skin and nail mycoses: treatment with ketoconazole, a new oral antimycotic agent. Mykosen. 1979 Aug;22(8):274–278. doi: 10.1111/j.1439-0507.1979.tb01757.x. [DOI] [PubMed] [Google Scholar]
- Chang T. Y., Telakowski C., Heuvel W. V., Alberts A. W., Vagelos P. R. Isolation and partial characterization of a cholesterol-requiring mutant of Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1977 Mar;74(3):832–836. doi: 10.1073/pnas.74.3.832. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Demel R. A., Bruckdorfer K. R., van Deenen L. L. The effect of sterol structure on the permeability of lipomes to glucose, glycerol and Rb + . Biochim Biophys Acta. 1972 Jan 17;255(1):321–330. doi: 10.1016/0005-2736(72)90031-4. [DOI] [PubMed] [Google Scholar]
- Heeres J., Backx L. J., Mostmans J. H., Van Cutsem J. Antimycotic imidazoles. part 4. Synthesis and antifungal activity of ketoconazole, a new potent orally active broad-spectrum antifungal agent. J Med Chem. 1979 Aug;22(8):1003–1005. doi: 10.1021/jm00194a023. [DOI] [PubMed] [Google Scholar]
- Henry M. J., Sisler H. D. Effects of miconazole and dodecylimidazole on sterol biosynthesis in Ustilago maydis. Antimicrob Agents Chemother. 1979 Apr;15(4):603–607. doi: 10.1128/aac.15.4.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kroon P. A., Kainosho M., Chan S. I. State of molecular motion of cholesterol in lecithin bilayers. Nature. 1975 Aug 14;256(5518):582–584. doi: 10.1038/256582a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Levine H. B., Cobb J. M. Oral therapy for experimental coccidioidomycosis with R41 400 (ketoconazole), a new imidazole. Am Rev Respir Dis. 1978 Oct;118(4):715–721. doi: 10.1164/arrd.1978.118.4.715. [DOI] [PubMed] [Google Scholar]
- Thienpont D., Van Cutsem J., Van Gerven F., Heeres J., Janssen P. A. Ketoconazole -- a new broad spectrum orally active antimycotic. Experientia. 1979 May 15;35(5):606–607. doi: 10.1007/BF01960348. [DOI] [PubMed] [Google Scholar]
- Van Den Bossche H., Willemsens G., Van Cutsem J. M. The action of miconazole of the growth of Candida albicans. Sabouraudia. 1975 Mar;13(Pt 1):63–73. [PubMed] [Google Scholar]
- Yeagle P. L., Martin R. B., Lala A. K., Lin H. K., Bloch K. Differential effects of cholesterol and lanosterol on artificial membranes. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4924–4926. doi: 10.1073/pnas.74.11.4924. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van den Bossche H., Willemsens G., Cools W., Lauwers W. F., Le Jeune L. Biochemical effects of miconazole on fungi. II. Inhibition of ergosterol biosynthesis in Candida albicans. Chem Biol Interact. 1978 Apr;21(1):59–78. doi: 10.1016/0009-2797(78)90068-6. [DOI] [PubMed] [Google Scholar]