Promising Antifungal Molecules against Mucormycosis Agents Identified from Pandemic Response Box ® : In Vitro and In Silico Analyses

Mucormycosis is considered concerning invasive fungal infections due to its high mortality rates, difficult diagnosis and limited treatment approaches. Mucorales species are highly resistant to many antifungal agents and the search for alternatives is an urgent need. In the present study, a library...

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Published in:Journal of fungi (Basel) 2023-01, Vol.9 (2), p.187
Main Authors: Xisto, Mariana Ingrid Dutra da Silva, Rollin-Pinheiro, Rodrigo, de Castro-Almeida, Yuri, Dos Santos-Freitas, Giulia Maria Pires, Rochetti, Victor Pereira, Borba-Santos, Luana Pereira, da Silva Fontes, Yasmin, Ferreira-Pereira, Antonio, Rozental, Sonia, Barreto-Bergter, Eliana
Format: Article
Language:English
Subjects:
Antifungal agents
Auranofin
biofilm
Biofilms
Cell walls
Coronaviruses
COVID-19
Cytology
Depolarization
Drugs
in silico analyses
Libraries
Malaria
Membrane potential
Membrane structure
Mitochondria
Mucormycosis
Oxidative stress
Pandemic Response Box
Pandemics
Pathogens
Posaconazole
Rhizopus
Scanning electron microscopy
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Summary:Mucormycosis is considered concerning invasive fungal infections due to its high mortality rates, difficult diagnosis and limited treatment approaches. Mucorales species are highly resistant to many antifungal agents and the search for alternatives is an urgent need. In the present study, a library with 400 compounds called the Pandemic Response Box was used and four compounds were identified: alexidine and three non-commercial molecules. These compounds showed anti-biofilm activity, as well as alterations in fungal morphology and cell wall and plasma membrane structure. They also induced oxidative stress and mitochondrial membrane depolarization. In silico analysis revealed promising pharmacological parameters. These results suggest that these four compounds are potent candidates to be considered in future studies for the development of new approaches to treat mucormycosis.
ISSN:2309-608X
2309-608X
DOI:10.3390/jof9020187