TY - JOUR
T1 - N,N′-diaryl-bishydrazones in a biphenyl platform
T2 - Broad spectrum antifungal agents
AU - Thamban Chandrika, Nishad
AU - Dennis, Emily K.
AU - Shrestha, Sanjib K.
AU - Ngo, Huy X.
AU - Green, Keith D.
AU - Kwiatkowski, Stefan
AU - Deaciuc, Agripina Gabriela
AU - Dwoskin, Linda P.
AU - Watt, David S.
AU - Garneau-Tsodikova, Sylvie
N1 - Publisher Copyright:
© 2018 Elsevier Masson SAS
PY - 2019/2/15
Y1 - 2019/2/15
N2 - 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.
AB - 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.
KW - Aspergillus sp.
KW - Candida albicans
KW - Cytotoxicity
KW - Hemolysis
KW - Non-albicans Candida
KW - hERG channel
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UR - http://www.scopus.com/inward/citedby.url?scp=85059156922&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2018.12.042
DO - 10.1016/j.ejmech.2018.12.042
M3 - Article
C2 - 30597328
AN - SCOPUS:85059156922
SN - 0223-5234
VL - 164
SP - 273
EP - 281
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -