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Chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of Cryptococcus neoformans.

Publication ,  Journal Article
Helsel, ME; White, EJ; Razvi, SZA; Alies, B; Franz, KJ
Published in: Metallomics : integrated biometal science
January 2017

A panel of iron (Fe) and copper (Cu) chelators was screened for growth inhibitory activity against the fungal pathogen Cryptococcus neoformans. Select bidentate metal-binding ligands containing mixed O,S or O,N donor atoms were identified as agents that induce cell killing in a Cu-dependent manner. Conversely, structurally similar ligands with O,O donor atoms did not inhibit C. neoformans growth regardless of Cu status. Studies of Cu(ii) and Cu(i) binding affinity, lipophilicity, and growth recovery assays of Cu-import deficient cells identified lipophilicity of thermodynamically stable CuIIL2 complexes as the best predictor of antifungal activity. These same complexes induce cellular hyperaccumulation of Zn and Fe in addition to Cu. The results described here present the utility of appropriate metal-binding ligands as potential antifungal agents that manipulate cellular metal balance as an antimicrobial strategy.

Duke Scholars

Published In

Metallomics : integrated biometal science

DOI

EISSN

1756-591X

ISSN

1756-5901

Publication Date

January 2017

Volume

9

Issue

1

Start / End Page

69 / 81

Related Subject Headings

  • Molecular Structure
  • Humans
  • Cryptococcus neoformans
  • Cryptococcosis
  • Copper
  • Chelating Agents
  • Antifungal Agents
  • Analytical Chemistry
  • 34 Chemical sciences
  • 03 Chemical Sciences
 

Citation

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Helsel, M. E., White, E. J., Razvi, S. Z. A., Alies, B., & Franz, K. J. (2017). Chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of Cryptococcus neoformans. Metallomics : Integrated Biometal Science, 9(1), 69–81. https://doi.org/10.1039/c6mt00172f
Helsel, Marian E., Elizabeth J. White, Sayyeda Zeenat A. Razvi, Bruno Alies, and Katherine J. Franz. “Chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of Cryptococcus neoformans.Metallomics : Integrated Biometal Science 9, no. 1 (January 2017): 69–81. https://doi.org/10.1039/c6mt00172f.
Helsel ME, White EJ, Razvi SZA, Alies B, Franz KJ. Chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of Cryptococcus neoformans. Metallomics : integrated biometal science. 2017 Jan;9(1):69–81.
Helsel, Marian E., et al. “Chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of Cryptococcus neoformans.Metallomics : Integrated Biometal Science, vol. 9, no. 1, Jan. 2017, pp. 69–81. Epmc, doi:10.1039/c6mt00172f.
Helsel ME, White EJ, Razvi SZA, Alies B, Franz KJ. Chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of Cryptococcus neoformans. Metallomics : integrated biometal science. 2017 Jan;9(1):69–81.
Journal cover image

Published In

Metallomics : integrated biometal science

DOI

EISSN

1756-591X

ISSN

1756-5901

Publication Date

January 2017

Volume

9

Issue

1

Start / End Page

69 / 81

Related Subject Headings

  • Molecular Structure
  • Humans
  • Cryptococcus neoformans
  • Cryptococcosis
  • Copper
  • Chelating Agents
  • Antifungal Agents
  • Analytical Chemistry
  • 34 Chemical sciences
  • 03 Chemical Sciences