Mode of action of 5-fluorocytosine

Robert B. Diasio, John E. Bennett, Charles E. Myers

Research output: Contribution to journalArticle

Abstract

A 5-fluorocytosine-sensitive isolate of Candida albicans was examined for the presence of thymidylate synthetase activity and 5-fluoro-2′-deoxyuridylic acid in the presence and absence of a growth-inhibiting concentration of 5-fluorocytosine. Initial studies demonstrated thymidylate synthetase activity in a crude homogenate prepared from this isolate. This activity could be inhibited by preincubating the homogenate with 5-fluoro-2′-deoxyuridylic acid. Evidence is presented suggesting that the inhibition of this enzyme is irreversible. Later studies measured thymidylate synthetase activity and 5-fluoro-2′-deoxyuridylic acid levels in homogenates prepared from harvested C. albicans after varying intervals of exposure to 100 μg/ml of 5-fluorocytosine. Thymidylate synthetase activity was observed to be 20 per cent of control after 1 hr of exposure to 5-FC, remaining decreased through the remainder of the 24 hr. 5-fluoro-2′-deoxyuridylate was measurable at all of the time points examined in the fungal cells exposed to 5-fluorocytosine in levels from 2 to 40 pmoles/μg of DNA while no evidence was found for this compound in the controls. In light of these findings, it is suggested that inhibition of thymidylate synthetase activity by endogenously synthesized 5-fluoro-2′-deoxyuridylic acid is a possible mechanism by which 5-fluorocytosine exerts its antifungal effect.

Original languageEnglish (US)
Pages (from-to)703-707
Number of pages5
JournalBiochemical Pharmacology
Volume27
Issue number5
DOIs
StatePublished - Mar 1 1978
Externally publishedYes

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Flucytosine
Thymidylate Synthase
Candida albicans
Candida
2'-deoxyuridylic acid
DNA
Enzymes
Growth

ASJC Scopus subject areas

  • Pharmacology

Cite this

Diasio, R. B., Bennett, J. E., & Myers, C. E. (1978). Mode of action of 5-fluorocytosine. Biochemical Pharmacology, 27(5), 703-707. https://doi.org/10.1016/0006-2952(78)90507-5

Mode of action of 5-fluorocytosine. / Diasio, Robert B.; Bennett, John E.; Myers, Charles E.

In: Biochemical Pharmacology, Vol. 27, No. 5, 01.03.1978, p. 703-707.

Research output: Contribution to journalArticle

Diasio, RB, Bennett, JE & Myers, CE 1978, 'Mode of action of 5-fluorocytosine', Biochemical Pharmacology, vol. 27, no. 5, pp. 703-707. https://doi.org/10.1016/0006-2952(78)90507-5
Diasio, Robert B. ; Bennett, John E. ; Myers, Charles E. / Mode of action of 5-fluorocytosine. In: Biochemical Pharmacology. 1978 ; Vol. 27, No. 5. pp. 703-707.
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