Discovery of uracil-based histone deacetylase inhibitors able to reduce acquired antifungal resistance and trailing growth in Candida albicans

Antonello Mai, Dante Rotili, Silvio Massa, Gerald Brosch, Giovanna Simonetti, Claudio Passariello, Anna Teresa Palamara

Research output: Contribution to journalArticlepeer-review

Abstract

Among fungal pathogens such as Candida albicans, acquired drug resistance has not been associated with plasmids or other transferable elements, but it is thought to involve primarily mutations and genetic or epigenetic phenomena. This prompted us to test some histone deacetylase inhibitors (HDACi) from our library, in combination with fluconazole, against C. albicans strains in vitro. Among the tested compounds, the two chloro-containing uracil-hydroxamates 1c and 1d showed a strong reduction of the MIC values on Candida strains that show the trailing growth effect. In this assay, 1c,d were more potent than SAHA, a well-known HDAC inhibitor, in reducing the Candida growth. More interestingly, 1c,d as well as SAHA were able to inhibit the fluconazole-induced resistance induction in Candida cultures.

Original languageEnglish
Pages (from-to)1221-1225
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number5
DOIs
Publication statusPublished - Mar 1 2007

Keywords

  • Antifungal resistance
  • Fluconazole
  • Histone deacetylase inhibitors
  • Trailing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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