Oral clioquinol is effective in the treatment of a fly model of Candida systemic infection.

BACKGROUND: Clioquinol was used in the 1950s-1970s as antimicrobial but its oral formulations were withdrawn from the market due to suspected neurotoxicity.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: 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: 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: 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-1 . Effective concentration found in modeling indicated that clioquinol was highly effective against C. albicans (0.306 μg ml-1 ) in easily achievable serum levels; and clioquinol rapidly achieved kill rate reaching the maximum effect after 13 h.

CONCLUSIONS: These results support the potential of clioquinol to be used as a systemic antifungal agent. This article is protected by copyright. All rights reserved.