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 journalArticlepeer-review

4 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 languageEnglish
Pages (from-to)124-133
Number of pages10
JournalChemMedChem
Volume16
Issue number1
DOIs
StatePublished - Jan 8 2021

Bibliographical note

Funding Information:
The work was supported by start‐up funds from the College of Pharmacy at the University of Kentucky (to S.G.‐T.). D.S.W. was supported by NIH R01 CA172379, the Office of the Dean of the College of Medicine, the Markey Cancer Center, the Center for Pharmaceutical Research and Innovation (CPRI) in the College of Pharmacy, NIH P20 RR020171 from the National Institute of General Medical Sciences, NIH P20GM130456, and the National Center for Advancing Translational Science (UL1 TR000117 and UL1 TR001998). This manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NSF, or of the NIGMS. We also thank Sarah A. Foree for help with determining some MIC values as a part of the University of Kentucky SURP. We are also grateful to writers at The New York Times who sparked our interest in finding treatments for Candida auris and whose commitment to discovery and the truth matches our own.

Funding Information:
The work was supported by start-up funds from the College of Pharmacy at the University of Kentucky (to S.G.-T.). D.S.W. was supported by NIH R01 CA172379, the Office of the Dean of the College of Medicine, the Markey Cancer Center, the Center for Pharmaceutical Research and Innovation (CPRI) in the College of Pharmacy, NIH P20 RR020171 from the National Institute of General Medical Sciences, NIH P20GM130456, and the National Center for Advancing Translational Science (UL1 TR000117 and UL1 TR001998). This manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NSF, or of the NIGMS. We also thank Sarah A. Foree for help with determining some MIC values as a part of the University of Kentucky SURP. We are also grateful to writers at The New York Times who sparked our interest in finding treatments for Candida auris and whose commitment to discovery and the truth matches our own.

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
  • Pharmacology, Toxicology and Pharmaceutics (all)
  • Organic Chemistry

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