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Metal Complexes as Antifungals? From a Crowd-Sourced Compound Library to the First ${In Vivo}$ Experiments

Frei, Angelo ; Elliott, Alysha G.; Kan, Alex; Dinh, Hue; Bräse, Stefan 1,2; Bruce, Alice E.; Bruce, Mitchell R.; Chen, Feng; Humaidy, Dhirgam; Jung, Nicole 1,3; King, A. Paden; Lye, Peter G.; Maliszewska, Hanna K.; Mansour, Ahmed M.; Matiadis, Dimitris; Muñoz, María Paz; Pai, Tsung-Yu; Pokhrel, Shyam; Sadler, Peter J.; ... mehr

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. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000151806
Veröffentlicht am 03.11.2022
Originalveröffentlichung
DOI: 10.1021/jacsau.2c00308
Scopus
Zitationen: 28
Dimensions
Zitationen: 37
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Institut für Organische Chemie (IOC)
Karlsruhe Nano Micro Facility (KNMF)
Publikationstyp Zeitschriftenaufsatz
Publikationsdatum 24.10.2022
Sprache Englisch
Identifikator ISSN: 0002-7863, 1520-5126, 1943-2984
KITopen-ID: 1000151806
HGF-Programm 43.33.11 (POF IV, LK 01) Adaptive and Bioinstructive Materials Systems
Erschienen in Journal of the American Chemical Society
Verlag ACS Publications
Band 2
Heft 10
Seiten 2277–2294
Vorab online veröffentlicht am 23.09.2022
Nachgewiesen in Dimensions
Scopus
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