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Non-toxic Cobalt(III) Schiff Base Complexes with Broad Spectrum Antifungal Activity

preprint
submitted on 30.07.2020 and posted on 30.07.2020 by 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.

Funding

Wellcome Trust Strategic Funding Award: 104797/Z/14/Z

The University of Queensland Strategic Funding Award

National Institute of Health, National Institute of General Medical Sciences, Chemical Biology Interface (CBI) Training Grant (grant number T32GM008500)

Swiss National Science Foundation Early Postdoc. Mobility fellowship (P2ZHP2_177997)

Wellcome Trust Strategic Grant WT1104797/Z/14/Z

Australian Research Council (ARC) DECRA fellowship (DE180100929)

History

Email Address of Submitting Author

angelo.frei.ch@gmail.com

Institution

The University of Queensland

Country

Australia

ORCID For Submitting Author

0000-0001-6169-2491

Declaration of Conflict of Interest

no conflict of interest

Version Notes

Version 1.0

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