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Distorted Gold(I)-Phosphine Complexes as Antifungal Agents.
Emily K Dennis1, Jong Hyun Kim2, Sean Parkin2
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
Journal of Medicinal Chemistry
|December 17, 2019
Summary
Gold(I)-phosphine complexes show potent antifungal activity against serious fungal infections. Two square-planar gold complexes are effective against multidrug-resistant Candida auris, offering new therapeutic potential.
Area of Science:
- Medicinal Chemistry
- Mycology
- Inorganic Chemistry
Background:
- Fungal infections like candidiasis and aspergillosis are significant nosocomial threats.
- Emerging resistance to current antifungal drugs necessitates novel therapeutic strategies.
- Inorganic compounds offer unexplored potential for treating fungal infections.
Purpose of the Study:
- To investigate the antifungal activity of gold(I)-phosphine complexes against a broad range of fungal pathogens.
- To evaluate the efficacy of linear and square-planar gold(I) complexes against clinically relevant fungal species.
- To assess the potential of gold complexes against multidrug-resistant fungi, particularly Candida auris.
Main Methods:
- Screening of 28 fungal strains including Candida, Cryptococcus, Aspergillus, and Fusarium species.
- Evaluation of linear and square-planar gold(I)-phosphine complexes.
- Characterization using time-kill studies, cytotoxicity, and hemolysis assays.
- Assessment of whole-cell uptake and potential for resistance development.
Main Results:
- Two square-planar gold(I) complexes demonstrated broad-spectrum antifungal activity.
- These complexes exhibited potent effects against Candida auris, a multidrug-resistant emerging pathogen.
- Further studies characterized the biological activity, uptake, and resistance profiles.
Conclusions:
- Gold(I)-phosphine complexes, particularly square-planar structures, represent a promising new class of antifungal agents.
- These compounds show significant potential for combating challenging fungal infections, including those caused by multidrug-resistant strains like Candida auris.
- Further development could lead to novel treatments for invasive fungal diseases.
