A novel naphthoquinone derivative shows selective antifungal activity against Sporothrix yeasts and biofilms.
Dimorphic fungi
Lawsone
Sporothrix brasiliensis
Sporothrix schenckii
Sporotrichosis
Journal
Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]
ISSN: 1678-4405
Titre abrégé: Braz J Microbiol
Pays: Brazil
ID NLM: 101095924
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
28
04
2021
accepted:
14
02
2022
pubmed:
9
3
2022
medline:
3
6
2022
entrez:
8
3
2022
Statut:
ppublish
Résumé
Sporotrichosis is a subcutaneous mycosis that affects humans and animals, with few therapeutic options available in the pharmaceutical market. We screened the in vitro antifungal activity of fourteen 1,4-naphthoquinones derivative compounds against Sporothrix brasiliensis and Sporothrix schenckii, the main etiological agents of sporotrichosis in Latin America. The most active compound was selected for further studies exploring its antibiofilm activity, effects on yeast morphophysiology, interaction with itraconazole, and selectivity to fungal cells. Among the fourteen 1,4-naphthoquinones tested, naphthoquinone 5, a silver salt of lawsone, was the most active compound. Naphthoquinone 5 was able to inhibit Sporothrix biofilms and induced ROS accumulation, mitochondrial disturbances, and severe plasmatic membrane damage in fungal cells. Furthermore, naphthoquinone 5 was ten times more selective towards fungal cells than fibroblast, and the combination of itraconazole with naphthoquinone 5 improved the inhibitory activity of the azole. Combined, the data presented here indicate that the silver salt naphthoquinone 5 exerts promising in vitro activity against the two main agents of sporotrichosis with important antibiofilm activity and a good toxicity profile, suggesting it is a promising molecule for the development of a new family of antifungals.
Identifiants
pubmed: 35258797
doi: 10.1007/s42770-022-00725-1
pii: 10.1007/s42770-022-00725-1
pmc: PMC9151959
doi:
Substances chimiques
Antifungal Agents
0
Naphthoquinones
0
Itraconazole
304NUG5GF4
Silver
3M4G523W1G
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
749-758Informations de copyright
© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.
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