Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA; Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA.
Eur J Med Chem. 2019 Feb 15;164:273-281. doi: 10.1016/j.ejmech.2018.12.042. Epub 2018 Dec 18.
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.
[N，N'-二芳基]联苯-3,4'-二醛、[1,1'-联苯]-4,4'-二醛和 4,4'-双乙酰基-1,1'-联苯的二酰肼表现出对广谱丝状和非丝状真菌的优异抗真菌活性。与之前报道的 N，N'-二氨基二酰肼和 N-脒基-N'-芳基二酰肼相比，这些 N，N'-二芳基联苯二酰肼没有抗菌活性。候选药物 4,4'-双((E)-1-(2-(4-氟苯基)腙基)乙基)-1,1'-联苯，在浓度等于或低于对照抗真菌剂（伏立康唑）的浓度下对鼠红细胞的溶血作用较小，在时间杀伤研究中具有抑菌作用，并且对 hERG 抑制没有哺乳动物细胞毒性和毒性。
