Resistance to currently available antifungal drugs has quietly been on the rise but overshadowed by the alarming spread of antibacterial resistance. There is a striking lack of attention to the threat of drug resistant fungal infections, with only a handful of new drugs currently in development. Given that metal complexes have proven to be useful new chemotypes in the fight against diseases such as cancer, malaria, and bacterial infections, it stands to reason to explore their possible utility in treating fungal infections. Herein we report a series of cobalt(III) Schiff base complexes with broad spectrum antifungal activity. Some of these complexes (1-3) show minimum inhibitory concentrations (MIC) in the low micro- to nanomolar range against a series of Candida and Cryptococcus yeasts. Additionally, we demonstrate that these compounds show no cytotoxicity against both bacterial and human cells. Finally, we report first in vivo toxicity data on these compounds in Galleria mellonella, showing that doses as high as 266 mg/kg are tolerated without adverse effects, paving the way for further in vivo studies of these complexes.


中文翻译：

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具有广谱抗真菌活性的无毒钴（III）希夫碱配合物

对目前可用的抗真菌药物的耐药性一直在悄然上升，但由于令人震惊的抗菌药物耐药性的传播而被掩盖了。对耐药性真菌感染的威胁非常缺乏关注，目前仅开发了少数新药。鉴于金属配合物已被证明是抗击癌症，疟疾和细菌感染等疾病的新化学类型，因此有理由探索其在治疗真菌感染中的可能用途。本文中我们报道了一系列具有广谱抗真菌活性的钴（III）席夫碱配合物。这些复合物（1-3）中的一些对一系列念珠菌和隐球菌酵母菌显示出最低的抑制浓度（MIC），其最低抑制浓度（MIC）在低微纳摩尔范围内。另外，我们证明这些化合物对细菌和人细胞均无细胞毒性。最后，我们首次报道了关于在马六甲酸牛奶中这些化合物的体内毒性数据，表明可以耐受高达266 mg / kg的剂量而无不良影响，为进一步研究这些复合物铺平了道路。