Antifungal activity and toxicological parameters of 8-hydroxyquinoline-5-sulfonamides using alternative animal models

J Appl Microbiol. 2021 Jun;130(6):1925-1934. doi: 10.1111/jam.14915. Epub 2020 Nov 22.

Abstract

Aim: The purpose of this study was to evaluate the antifungal activity and toxicological parameters of 8-hydroxyquinoline derivatives PH151 and PH153 using alternative animal models, to understand their behaviour when subjected to in vivo experiments.

Methods and results: We used Toll-deficient Drosophila melanogaster to test the protective effect of compounds against Candida albicans infection. Toxicological parameters were investigated in chicken and zebrafish embryos. PH151 and PH153 showed low toxicity and the treated flies with these compounds had a significantly higher survival rate than untreated flies after 7 days of infection. The compounds did not cause interruption of chicken embryogenesis. Zebrafish embryos exposed to compounds showed dose-dependent toxicity.

Conclusions: The data supported the potential of PH151 and PH153 for the treatment of systemic candidiasis and demonstrated to be appropriate drug candidates for further studies using mammalian models.

Significance and impact of the study: The increased incidence of Candida infections resistant to antifungals currently available requires acceleration of the discovery of new agents with properties of inhibiting this fungal pathogen. In this study, we have described the antifungal potential and toxicity of two 8-hydroxyquinoline derivatives using in vivo alternative models, and the results confirm their potential to be developed as new drug candidates.

Keywords: Drosophila melanogaster; 8-hydroxyquinoline derivatives; Candida spp.; chicken embryo; zebrafish.

MeSH terms

  • Animals
  • Antifungal Agents / chemistry
  • Antifungal Agents / therapeutic use*
  • Candida albicans / drug effects
  • Candidiasis / drug therapy*
  • Candidiasis / microbiology
  • Chick Embryo
  • Disease Models, Animal*
  • Drosophila melanogaster
  • Oxyquinoline / chemistry
  • Oxyquinoline / therapeutic use*
  • Sulfonamides / chemistry
  • Sulfonamides / therapeutic use*
  • Zebrafish

Substances

  • Antifungal Agents
  • Sulfonamides
  • Oxyquinoline