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.