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Oral clioquinol is effective in the treatment of a fly model of Candida systemic infection.
- Source :
-
Mycoses [Mycoses] 2019 May; Vol. 62 (5), pp. 475-481. Date of Electronic Publication: 2019 Mar 26. - Publication Year :
- 2019
-
Abstract
- Background: Clioquinol was used in the 1950s-1970s as antimicrobial but its oral formulations were withdrawn from the market due to suspected neurotoxicity.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.<br />Objectives: 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.<br />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.<br />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 <superscript>-1</superscript> . Effective concentration found in modelling indicated that clioquinol was highly effective against C. albicans (0.306 μg mL <superscript>-1</superscript> ) in easily achievable serum levels; clioquinol rapidly achieved kill rate reaching the maximum effect after 13 hours.<br />Conclusions: These results support the potential of clioquinol to be used as a systemic antifungal agent.<br /> (© 2019 Blackwell Verlag GmbH.)
- Subjects :
- Administration, Oral
Animals
Antifungal Agents adverse effects
Chick Embryo
Chickens
Clioquinol adverse effects
Disease Models, Animal
Drosophila melanogaster
Models, Theoretical
Treatment Outcome
Antifungal Agents administration & dosage
Candidiasis drug therapy
Clioquinol administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1439-0507
- Volume :
- 62
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Mycoses
- Publication Type :
- Academic Journal
- Accession number :
- 30600560
- Full Text :
- https://doi.org/10.1111/myc.12888