Distorted Gold(I)-Phosphine Complexes as Antifungal Agents

Emily K. Dennis; Jong Hyun Kim; Sean Parkin; Samuel G. Awuah; Sylvie Garneau-Tsodikova

doi:10.1021/acs.jmedchem.9b01436

Distorted Gold(I)-Phosphine Complexes as Antifungal Agents

Emily K. Dennis, Jong Hyun Kim, Sean Parkin, Samuel G. Awuah, Sylvie Garneau-Tsodikova

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Fungi cause serious nosocomial infections including candidiasis and aspergillosis, some of which display reduced susceptibility to current antifungals. Inorganic compounds have been found to be beneficial against various medical ailments but have yet to be applied to fungal infections. Here, we explore the activity of linear and square-planar gold(I)-phosphine complexes against a panel of 28 fungal strains including Candida spp., Cryptococcus spp., Aspergillus spp., and Fusarium spp. Notably, two square-planar gold(I) complexes with excellent broad-spectrum activity display potent antifungal effects against strains of Candida auris, an emerging multidrug-resistant fungus that presents a serious global health threat. To characterize the biological activity of these gold(I) complexes, we used a series of time-kill studies, cytotoxicity and hemolysis assays, as well as whole-cell uptake and development of resistance studies.

Original language	English
Pages (from-to)	2455-2469
Number of pages	15
Journal	Journal of Medicinal Chemistry
Volume	63
Issue number	5
DOIs	https://doi.org/10.1021/acs.jmedchem.9b01436
State	Published - Mar 12 2020

Bibliographical note

Funding Information:
This work was supported in part by a University of Kentucky Igniting Research Collaborations pilot grant, funded by the Vice President for Research and College Deans (to S.G.-T. and S.G.A.), and startup funds from the University of Kentucky (to S.G.-T. and S.G.A.). We also thank the University of Kentucky’s Environmental Research Training Laboratory (ERTL) for their assistance with the ICP-OES, Prof. Sidney Whiteheart for providing the red blood cells for the hemolysis studies, and Dr. Norman Lee of the Chemical Instrumentation Center at Boston University for mass spectrometry analysis. Crystallography at the University of Kentucky is supported by NSF MRI Award CHE1625732 (to S.P.).

Funding Information:
This work was supported in part by a University of Kentucky Igniting Research Collaborations pilot grant, funded by the Vice President for Research and College Deans (to S.G.-T. and S.G.A.), and startup funds from the University of Kentucky (to S.G.-T. and S.G.A.). We also thank the University of Kentucky?s Environmental Research Training Laboratory (ERTL) for their assistance with the ICP-OES, Prof. Sidney Whiteheart for providing the red blood cells for the hemolysis studies, and Dr. Norman Lee of the Chemical Instrumentation Center at Boston University for mass spectrometry analysis. Crystallography at the University of Kentucky is supported by NSF MRI Award CHE1625732 (to S.P.).

Publisher Copyright:
Copyright © 2019 American Chemical Society.

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/acs.jmedchem.9b01436

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title = "Distorted Gold(I)-Phosphine Complexes as Antifungal Agents",

abstract = "Fungi cause serious nosocomial infections including candidiasis and aspergillosis, some of which display reduced susceptibility to current antifungals. Inorganic compounds have been found to be beneficial against various medical ailments but have yet to be applied to fungal infections. Here, we explore the activity of linear and square-planar gold(I)-phosphine complexes against a panel of 28 fungal strains including Candida spp., Cryptococcus spp., Aspergillus spp., and Fusarium spp. Notably, two square-planar gold(I) complexes with excellent broad-spectrum activity display potent antifungal effects against strains of Candida auris, an emerging multidrug-resistant fungus that presents a serious global health threat. To characterize the biological activity of these gold(I) complexes, we used a series of time-kill studies, cytotoxicity and hemolysis assays, as well as whole-cell uptake and development of resistance studies.",

author = "Dennis, {Emily K.} and Kim, {Jong Hyun} and Sean Parkin and Awuah, {Samuel G.} and Sylvie Garneau-Tsodikova",

note = "Funding Information: This work was supported in part by a University of Kentucky Igniting Research Collaborations pilot grant, funded by the Vice President for Research and College Deans (to S.G.-T. and S.G.A.), and startup funds from the University of Kentucky (to S.G.-T. and S.G.A.). We also thank the University of Kentucky{\textquoteright}s Environmental Research Training Laboratory (ERTL) for their assistance with the ICP-OES, Prof. Sidney Whiteheart for providing the red blood cells for the hemolysis studies, and Dr. Norman Lee of the Chemical Instrumentation Center at Boston University for mass spectrometry analysis. Crystallography at the University of Kentucky is supported by NSF MRI Award CHE1625732 (to S.P.). Funding Information: This work was supported in part by a University of Kentucky Igniting Research Collaborations pilot grant, funded by the Vice President for Research and College Deans (to S.G.-T. and S.G.A.), and startup funds from the University of Kentucky (to S.G.-T. and S.G.A.). We also thank the University of Kentucky?s Environmental Research Training Laboratory (ERTL) for their assistance with the ICP-OES, Prof. Sidney Whiteheart for providing the red blood cells for the hemolysis studies, and Dr. Norman Lee of the Chemical Instrumentation Center at Boston University for mass spectrometry analysis. Crystallography at the University of Kentucky is supported by NSF MRI Award CHE1625732 (to S.P.). Publisher Copyright: Copyright {\textcopyright} 2019 American Chemical Society.",

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N2 - Fungi cause serious nosocomial infections including candidiasis and aspergillosis, some of which display reduced susceptibility to current antifungals. Inorganic compounds have been found to be beneficial against various medical ailments but have yet to be applied to fungal infections. Here, we explore the activity of linear and square-planar gold(I)-phosphine complexes against a panel of 28 fungal strains including Candida spp., Cryptococcus spp., Aspergillus spp., and Fusarium spp. Notably, two square-planar gold(I) complexes with excellent broad-spectrum activity display potent antifungal effects against strains of Candida auris, an emerging multidrug-resistant fungus that presents a serious global health threat. To characterize the biological activity of these gold(I) complexes, we used a series of time-kill studies, cytotoxicity and hemolysis assays, as well as whole-cell uptake and development of resistance studies.

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Distorted Gold(I)-Phosphine Complexes as Antifungal Agents

Abstract

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