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

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.

SUBMITTER: Thamban Chandrika N

PROVIDER: S-EPMC6351225 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Thamban Chandrika Nishad N Dennis Emily K EK Shrestha Sanjib K SK Ngo Huy X HX Green Keith D KD Kwiatkowski Stefan S Deaciuc Agripina Gabriela AG Dwoskin Linda P LP Watt David S DS Garneau-Tsodikova Sylvie S

European journal of medicinal chemistry 20181218

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'-biphen ...[more]

PMID: 30597328

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