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Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans.

Publication ,  Journal Article
Hunsaker, EW; McAuliffe, KJ; Franz, KJ
Published in: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry
August 2020

Azole antifungals are an important class of antifungal drugs due to their low cost, ability to be administered orally, and broad-spectrum activity. However, their widespread and long-term use have given rise to adaptation mechanisms that render these compounds less effective against common fungal pathogens, including Candida albicans. New antifungals are desperately needed as drug-resistant strains become more prevalent. We recently showed that copper supplementation potentiates the activity of the azole antifungal fluconazole against the opportunistic fungal pathogen C. albicans. Here, we report eight new azole analogues derived from fluconazole in which one triazole group has been replaced with a metal-binding group, a strategy designed to enhance potentiation of azole antifungal activity by copper. The bioactivity of all eight compounds was tested and compared to that of fluconazole. Three of the analogues showed activity against C. albicans and two had lower levels of trailing growth. One compound, Flu-TSCZ, was found to impact the levels, speciation, and bioavailability of cellular metals.

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Published In

Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry

DOI

EISSN

1432-1327

ISSN

0949-8257

Publication Date

August 2020

Volume

25

Issue

5

Start / End Page

729 / 745

Related Subject Headings

  • Microbial Sensitivity Tests
  • Metals, Heavy
  • Fluconazole
  • Coordination Complexes
  • Candida albicans
  • Biophysics
  • Antifungal Agents
  • 3402 Inorganic chemistry
  • 3101 Biochemistry and cell biology
  • 0601 Biochemistry and Cell Biology
 

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Hunsaker, E. W., McAuliffe, K. J., & Franz, K. J. (2020). Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans. Journal of Biological Inorganic Chemistry : JBIC : A Publication of the Society of Biological Inorganic Chemistry, 25(5), 729–745. https://doi.org/10.1007/s00775-020-01796-x
Hunsaker, Elizabeth W., Katherine J. McAuliffe, and Katherine J. Franz. “Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans.Journal of Biological Inorganic Chemistry : JBIC : A Publication of the Society of Biological Inorganic Chemistry 25, no. 5 (August 2020): 729–45. https://doi.org/10.1007/s00775-020-01796-x.
Hunsaker EW, McAuliffe KJ, Franz KJ. Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 2020 Aug;25(5):729–45.
Hunsaker, Elizabeth W., et al. “Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans.Journal of Biological Inorganic Chemistry : JBIC : A Publication of the Society of Biological Inorganic Chemistry, vol. 25, no. 5, Aug. 2020, pp. 729–45. Epmc, doi:10.1007/s00775-020-01796-x.
Hunsaker EW, McAuliffe KJ, Franz KJ. Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 2020 Aug;25(5):729–745.
Journal cover image

Published In

Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry

DOI

EISSN

1432-1327

ISSN

0949-8257

Publication Date

August 2020

Volume

25

Issue

5

Start / End Page

729 / 745

Related Subject Headings

  • Microbial Sensitivity Tests
  • Metals, Heavy
  • Fluconazole
  • Coordination Complexes
  • Candida albicans
  • Biophysics
  • Antifungal Agents
  • 3402 Inorganic chemistry
  • 3101 Biochemistry and cell biology
  • 0601 Biochemistry and Cell Biology