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Clioquinol was used in the 1950s-1970s as antimicrobial but its oral formulations were withdrawn from the market due to suspected neurotoxicity.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.

• Authors: Bruna Pippi, Simone Merkel, Keli Jaqueline Staudt, Mario Lettieri Teixeira, Bibiana Verlindo de Araújo, Régis Adriel Zanette, Saulo Fernandes Andrade, Alexandre Meneghello Fuentefria
• Journal: Mycoses (Mycoses) Vol. 62 Issue 5 Pg. 475-481 (May 2019) ISSN: 1439-0507 [Electronic] Germany
• PMID: 30600560 (Publication Type: Journal Article)
• Copyright: © 2019 Blackwell Verlag GmbH.

Chemical References

• Antifungal Agents
• Clioquinol

Topics

• Administration, Oral
• Animals
• Antifungal Agents (administration & dosage, adverse effects)
• Candidiasis (drug therapy)
• Chick Embryo
• Chickens
• Clioquinol (administration & dosage, adverse effects)
• Disease Models, Animal
• Drosophila melanogaster
• Models, Theoretical
• Treatment Outcome