Promising Antifungal Molecules against Mucormycosis Agents Identified from Pandemic Response Box ® : In Vitro and In Silico Analyses.
Mariana Ingrid Dutra da Silva XistoRodrigo Rollin-PinheiroYuri de Castro-AlmeidaGiulia Maria Pires Dos Santos-FreitasVictor Pereira RochettiLuana Pereira Borba-SantosYasmin da Silva FontesAntônio Ferreira-PereiraSonia RozentalEliana Barreto-BergterPublished in: Journal of fungi (Basel, Switzerland) (2023)
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.