Broad-Spectrum Antifungal Agents: Fluorinated Aryl- and Heteroaryl-Substituted Hydrazones

Nishad Thamban Chandrika; Emily K. Dennis; Katelyn R. Brubaker; Stefan Kwiatkowski; David S. Watt; Sylvie Garneau-Tsodikova

doi:10.1002/cmdc.202000626

Broad-Spectrum Antifungal Agents: Fluorinated Aryl- and Heteroaryl-Substituted Hydrazones

Nishad Thamban Chandrika, Emily K. Dennis, Katelyn R. Brubaker, Stefan Kwiatkowski, David S. Watt, Sylvie Garneau-Tsodikova

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

8 Scopus citations

Abstract

Fluorinated aryl- and heteroaryl-substituted monohydrazones displayed excellent broad-spectrum activity against various fungal strains, including a panel of clinically relevant Candida auris strains relative to a control antifungal agent, voriconazole (VRC). These monohydrazones displayed less hemolysis of murine red blood cells than that of VRC at the same concentrations, possessed fungicidal activity in a time-kill study, and exhibited no mammalian cell cytotoxicity. In addition, these monohydrazones prevented the formation of biofilms that otherwise block antibiotic effectiveness and did not trigger the development of resistance when exposed to C. auris AR Bank # 0390 over 15 passages.

Original language	English
Pages (from-to)	124-133
Number of pages	10
Journal	ChemMedChem
Volume	16
Issue number	1
DOIs	https://doi.org/10.1002/cmdc.202000626
State	Published - Jan 8 2021

Bibliographical note

Publisher Copyright:
© 2020 Wiley-VCH GmbH

Keywords

Biofilm
Candida auris
Cytotoxicity
Drug resistance
Hemolysis
Monohydrazones

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Drug Discovery
General Pharmacology, Toxicology and Pharmaceutics
Organic Chemistry

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10.1002/cmdc.202000626

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abstract = "Fluorinated aryl- and heteroaryl-substituted monohydrazones displayed excellent broad-spectrum activity against various fungal strains, including a panel of clinically relevant Candida auris strains relative to a control antifungal agent, voriconazole (VRC). These monohydrazones displayed less hemolysis of murine red blood cells than that of VRC at the same concentrations, possessed fungicidal activity in a time-kill study, and exhibited no mammalian cell cytotoxicity. In addition, these monohydrazones prevented the formation of biofilms that otherwise block antibiotic effectiveness and did not trigger the development of resistance when exposed to C. auris AR Bank # 0390 over 15 passages.",

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AU - Thamban Chandrika, Nishad

AU - Dennis, Emily K.

AU - Brubaker, Katelyn R.

AU - Kwiatkowski, Stefan

AU - Watt, David S.

AU - Garneau-Tsodikova, Sylvie

PY - 2021/1/8

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AB - Fluorinated aryl- and heteroaryl-substituted monohydrazones displayed excellent broad-spectrum activity against various fungal strains, including a panel of clinically relevant Candida auris strains relative to a control antifungal agent, voriconazole (VRC). These monohydrazones displayed less hemolysis of murine red blood cells than that of VRC at the same concentrations, possessed fungicidal activity in a time-kill study, and exhibited no mammalian cell cytotoxicity. In addition, these monohydrazones prevented the formation of biofilms that otherwise block antibiotic effectiveness and did not trigger the development of resistance when exposed to C. auris AR Bank # 0390 over 15 passages.

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KW - Cytotoxicity

KW - Drug resistance

KW - Hemolysis

KW - Monohydrazones

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Broad-Spectrum Antifungal Agents: Fluorinated Aryl- and Heteroaryl-Substituted Hydrazones

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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