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submitted on 30.07.2020 and posted on 30.07.2020by Angelo Frei, A. Paden King, Gabrielle J. Lowe, Amy K. Cain, Francesca L. Short, Hue Dinh, Alysha Elliott, Johannes Zuegg, Justin J. Wilson, Mark Blaskovich
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.