N,N′-diaryl-bishydrazones in a biphenyl platform: Broad spectrum antifungal agents

Nishad Thamban Chandrika, Emily K. Dennis, Sanjib K. Shrestha, Huy X. Ngo, Keith D. Green, Stefan Kwiatkowski, Agripina Gabriela Deaciuc, Linda P. Dwoskin, David S. Watt, Sylvie Garneau-Tsodikova

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

N,N′-Diaryl-bishydrazones of [1,1′-biphenyl]-3,4′-dicarboxaldehyde, [1,1′-biphenyl]-4,4′-dicarboxaldehyde, and 4,4′-bisacetyl-1,1-biphenyl exhibited excellent antifungal activity against a broad spectrum of filamentous and non-filamentous fungi. These N,N′-diaryl-bishydrazones displayed no antibacterial activity in contrast to previously reported N,N′-diamidino-bishydrazones and N-amidino-N′-aryl-bishydrazones. The leading candidate, 4,4′-bis((E)-1-(2-(4-fluorophenyl)hydrazono)ethyl)-1,1′-biphenyl, displayed less hemolysis of murine red blood cells at concentrations at or below that of a control antifungal agent (voriconazole), was fungistatic in a time-kill study, and possessed no mammalian cytotoxicity and no toxicity with respect to hERG inhibition.

Original languageEnglish
Pages (from-to)273-281
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume164
DOIs
StatePublished - Feb 15 2019

Bibliographical note

Funding Information:
This work was supported by startup funds from the College of Pharmacy at the University of Kentucky (to S.G.-T.). D.S.W. was supported by CA172379 from the NIH . D.S.W. was also supported by the Office of the Dean of the College of Medicine , by the Center for Pharmaceutical Research and Innovation in the College of Pharmacy , and by NIH Grant Number P30 GM110787 from the National Institute of General Medical Sciences to L. Hersh, PI. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the NIGMS. D.S.W. was also supported by the Office of the Assistant Secretary of Defense for Health Affairs , through the Prostate Cancer Research Program under Award No. W81XWH-16-1-0635 . Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.

Publisher Copyright:
© 2018 Elsevier Masson SAS

Keywords

  • Aspergillus sp.
  • Candida albicans
  • Cytotoxicity
  • Hemolysis
  • Non-albicans Candida
  • hERG channel

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'N,N′-diaryl-bishydrazones in a biphenyl platform: Broad spectrum antifungal agents'. Together they form a unique fingerprint.

Cite this