Activity of Metal-Azole Complexes Against Biofilms of
Candida albicans
Candida glabrata
antifungals
biofilms
drug optimization
metal-complexes
onychomycosis.
Journal
Current pharmaceutical design
ISSN: 1873-4286
Titre abrégé: Curr Pharm Des
Pays: United Arab Emirates
ID NLM: 9602487
Informations de publication
Date de publication:
2020
2020
Historique:
received:
27
09
2019
accepted:
21
01
2020
pubmed:
18
2
2020
medline:
1
12
2020
entrez:
18
2
2020
Statut:
ppublish
Résumé
Onychomycosis is a chronic nail infection caused by fungi frequently resistant to antifungal treatments. Recalcitrance in nail infections is a result of reduced antifungal penetration due to biofilm formation, combined with poor patient compliance with the treatment, which can be as long as 18 months. Metal-drug complexation is a widely used strategy to increase drug efficacy. Therefore, the aim of this work was to evaluate the antifungal and anti-biofilm activity of several metal-azole complexes against Candida albicans and Candida glabrata. Susceptibility assays and scanning electron microscopy were performed to determine the anti-biofilm activity of eight metal-azole complexes in vitro and ex-vivo, using human nail fragments. In vitro susceptibility assays showed that complexation of both Au(I) and Zn(II) to clotrimazole and ketoconazole improved the anti-biofilm activity compared to the azole alone. Using an ex-vivo model of biofilm formation on fragments of human nails, we also demonstrate the improved efficacy of metal-azole complexes against biofilms of C. albicans and C. glabrata that resembles the onychomycosis structure. Noteworthy, biofilms of C. glabrata were more susceptible to the optimized complexes than those of C. albicans. In conclusion, metal-azole complexes used in this work show promising anti-biofilm activity and further clinical studies should confirm its potential for the treatment of Candida-associated onychomycosis.
Sections du résumé
BACKGROUND
Onychomycosis is a chronic nail infection caused by fungi frequently resistant to antifungal treatments. Recalcitrance in nail infections is a result of reduced antifungal penetration due to biofilm formation, combined with poor patient compliance with the treatment, which can be as long as 18 months.
OBJECTIVE
Metal-drug complexation is a widely used strategy to increase drug efficacy. Therefore, the aim of this work was to evaluate the antifungal and anti-biofilm activity of several metal-azole complexes against Candida albicans and Candida glabrata.
METHODS
Susceptibility assays and scanning electron microscopy were performed to determine the anti-biofilm activity of eight metal-azole complexes in vitro and ex-vivo, using human nail fragments.
RESULTS
In vitro susceptibility assays showed that complexation of both Au(I) and Zn(II) to clotrimazole and ketoconazole improved the anti-biofilm activity compared to the azole alone. Using an ex-vivo model of biofilm formation on fragments of human nails, we also demonstrate the improved efficacy of metal-azole complexes against biofilms of C. albicans and C. glabrata that resembles the onychomycosis structure. Noteworthy, biofilms of C. glabrata were more susceptible to the optimized complexes than those of C. albicans.
CONCLUSION
In conclusion, metal-azole complexes used in this work show promising anti-biofilm activity and further clinical studies should confirm its potential for the treatment of Candida-associated onychomycosis.
Identifiants
pubmed: 32065088
pii: CPD-EPUB-104567
doi: 10.2174/1381612826666200217120321
doi:
Substances chimiques
Antifungal Agents
0
Azoles
0
Coordination Complexes
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1524-1531Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.