Oral clioquinol is effective in the treatment of a fly model of Candida systemic infection.
Drosophila melanogaster
8-hydroxyquinolines
Candida spp.
PK/PD modelling
antifungal
clioquinol
Journal
Mycoses
ISSN: 1439-0507
Titre abrégé: Mycoses
Pays: Germany
ID NLM: 8805008
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
revised:
06
12
2018
accepted:
27
12
2018
pubmed:
3
1
2019
medline:
21
5
2019
entrez:
3
1
2019
Statut:
ppublish
Résumé
Clioquinol was used in the 1950s-1970s as antimicrobial but its oral formulations were withdrawn from the market due to suspected neurotoxicity. Currently, there is possibility of repositioning of oral clioquinol formulations. To evaluate the antifungal activity and toxicological parameters of clioquinol and the other two 8-hydroxyquinoline derivatives using alternative animal models and to study the interaction dynamic of clioquinol with Candida albicans. We used Toll-deficient Drosophila melanogaster to test the protective effect of 8-hydroxyquinolines against C. albicans infection. Toxicological parameters were investigated in chicken embryo. A mathematical model-based analysis of the time-kill data of clioquinol was performed to obtain pharmacodynamic characteristics. Clioquinol fully protected D. melanogaster from the infection. The 8-hydroxyquinolines did not cause changes in opening of the beak and movement of the chicken embryo; however, clioquinol and compound 2 increased arterial pulsation. Compound 3 was lethal at 1 mg mL These results support the potential of clioquinol to be used as a systemic antifungal agent.
Sections du résumé
BACKGROUND
BACKGROUND
Clioquinol was used in the 1950s-1970s as antimicrobial but its oral formulations were withdrawn from the market due to suspected neurotoxicity. Currently, there is possibility of repositioning of oral clioquinol formulations.
OBJECTIVES
OBJECTIVE
To evaluate the antifungal activity and toxicological parameters of clioquinol and the other two 8-hydroxyquinoline derivatives using alternative animal models and to study the interaction dynamic of clioquinol with Candida albicans.
METHODS
METHODS
We used Toll-deficient Drosophila melanogaster to test the protective effect of 8-hydroxyquinolines against C. albicans infection. Toxicological parameters were investigated in chicken embryo. A mathematical model-based analysis of the time-kill data of clioquinol was performed to obtain pharmacodynamic characteristics.
RESULTS
RESULTS
Clioquinol fully protected D. melanogaster from the infection. The 8-hydroxyquinolines did not cause changes in opening of the beak and movement of the chicken embryo; however, clioquinol and compound 2 increased arterial pulsation. Compound 3 was lethal at 1 mg mL
CONCLUSIONS
CONCLUSIONS
These results support the potential of clioquinol to be used as a systemic antifungal agent.
Substances chimiques
Antifungal Agents
0
Clioquinol
7BHQ856EJ5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
475-481Subventions
Organisme : Brazilian agencies Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Organisme : Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul
ID : FAPERGS - EDITAL 04/2016 - PRONUPEQ 2016
Informations de copyright
© 2019 Blackwell Verlag GmbH.