The Library
Metal complexes as antifungals? From a crowd-sourced compound library to the first in vivo experiments
Tools
(2022) Metal complexes as antifungals? From a crowd-sourced compound library to the first in vivo experiments. JACS Au, 2 (10). pp. 2277-2294. doi:10.1021/jacsau.2c00308 ISSN 2691-3704.
|
PDF
WRAP-metal-complexes-antifungals-crowd-sourced-compound-library-first-in-vivo-experiments-Sadler-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (3526Kb) | Preview |
Official URL: https://doi.org/10.1021/jacsau.2c00308
Abstract
There are currently fewer than 10 antifungal drugs in clinical development, but new fungal strains that are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents. In this work, we report the evaluation of 1039 metal-containing compounds that were screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD). We show that 20.9% of all metal compounds tested have antimicrobial activity against two representative Candida and Cryptococcus strains compared with only 1.1% of the >300,000 purely organic molecules tested through CO-ADD. We identified 90 metal compounds (8.7%) that show antifungal activity while not displaying any cytotoxicity against mammalian cell lines or hemolytic properties at similar concentrations. The structures of 21 metal complexes that display high antifungal activity (MIC ≤1.25 μM) are discussed and evaluated further against a broad panel of yeasts. Most of these have not been previously tested for antifungal activity. Eleven of these metal complexes were tested for toxicity in the Galleria mellonella moth larva model, revealing that only one compound showed signs of toxicity at the highest injected concentration. Lastly, we demonstrated that the organo-Pt(II) cyclooctadiene complex Pt1 significantly reduces fungal load in an in vivoG. mellonella infection model. These findings showcase that the structural and chemical diversity of metal-based compounds can be an invaluable tool in the development of new drugs against infectious diseases.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Subjects: | Q Science > QD Chemistry R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology |
||||||||||||||||||||||||||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||||||||||||||||||||||||||||||||||||
SWORD Depositor: | Library Publications Router | ||||||||||||||||||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Mycoses, Antifungal agents, Fungi -- Effect of drugs on, Metal complexes, Drug resistance in microorganisms -- Effect of drugs on | ||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | JACS Au | ||||||||||||||||||||||||||||||||||||||||||
Publisher: | American Chemical Society | ||||||||||||||||||||||||||||||||||||||||||
ISSN: | 2691-3704 | ||||||||||||||||||||||||||||||||||||||||||
Official Date: | 24 October 2022 | ||||||||||||||||||||||||||||||||||||||||||
Dates: |
|
||||||||||||||||||||||||||||||||||||||||||
Volume: | 2 | ||||||||||||||||||||||||||||||||||||||||||
Number: | 10 | ||||||||||||||||||||||||||||||||||||||||||
Page Range: | pp. 2277-2294 | ||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1021/jacsau.2c00308 | ||||||||||||||||||||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||||||||||||||
Date of first compliant deposit: | 14 November 2022 | ||||||||||||||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 15 November 2022 | ||||||||||||||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
|
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year