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

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BACKGROUND:Clioquinol was used in the 1950s-1970s as antimicrobial but its oral formulations were withdrawn from the market due to suspected neurotoxicity.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. 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 modelling indicated that clioquinol was highly effective against C. albicans (0.306 μg mL-1 ) in easily achievable serum levels; clioquinol rapidly achieved kill rate reaching the maximum effect after 13 hours. CONCLUSIONS:These results support the potential of clioquinol to be used as a systemic antifungal agent.

journal_name

Mycoses

journal_title

Mycoses

authors

Pippi B,Merkel S,Staudt KJ,Teixeira ML,de Araújo BV,Zanette RA,Andrade SF,Fuentefria AM

doi

10.1111/myc.12888

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

475-481

issue

5

eissn

0933-7407

issn

1439-0507

journal_volume

62

pub_type

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