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Quantifying the Antifungal Activity of Peptides Against Candida albicans
Published on: January 13, 2023
Antifungal Activity of 8-Hydroxyquinoline Derivatives Against Candida auris, Candida haemulonii, Cryptococcus
Maria Eduarda Krummenauer1,2, Matheus da Silva Camargo1,2, Caroline de Bem Gentz3
1Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, Porto Alegre 91501-970, RS, Brazil.
Abstract:
Invasive fungal infections and the emergence of antifungal resistance pose significant challenges to public health. This study evaluates the antifungal activity of two 8-hydroxyquinoline derivatives, PH265 and PH276, against Cryptococcus spp., Candida auris, and Candida haemulonii. Using the EUCAST protocol, both compounds demonstrated broad-spectrum antifungal activity, with MICs ranging from 0.5 to 8 μg/mL. PH276 exhibited synergistic effects with fluconazole and caspofungin against C. haemulonii (FIC ≤ 0.5). The derivatives inhibited C. neoformans biofilm formation at higher concentrations and modulated polysaccharide capsule formation in Cryptococcus spp. In vivo toxicity assays in Tenebrio molitor, Galleria mellonella, and Caenorhabditis elegans revealed no significant adverse effects, with survival rates comparable to controls. These findings highlight PH265 and PH276 as promising antifungal agents with biofilm-disrupting properties, capsule-modulating effects, and low toxicity, supporting their potential for therapeutic development.
Insights
Two novel 8-hydroxyquinoline derivatives, PH265 and PH276, show broad-spectrum antifungal activity against resistant fungi like Candida auris. These compounds also disrupt biofilms and have low toxicity, indicating potential for new antifungal therapies.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Invasive fungal infections (IFIs) are a growing public health concern due to increasing antifungal resistance.
- Emerging pathogens such as *Candida auris* present unique treatment challenges.
- Novel therapeutic agents are urgently needed to combat resistant fungal infections.
Purpose of the Study:
- To evaluate the *in vitro* and *in vivo* antifungal potential of two 8-hydroxyquinoline derivatives, PH265 and PH276.
- To assess their activity against clinically relevant fungal species, including *Cryptococcus* spp., *Candida auris*, and *Candida haemulonii*.
- To investigate their effects on fungal biofilm formation and capsule modulation, as well as their toxicity profiles.
Main Methods:
- Minimum Inhibitory Concentrations (MICs) were determined using the EUCAST protocol.
- Synergistic effects were evaluated in combination with fluconazole and caspofungin.
- Biofilm inhibition and capsule modulation assays were performed.
- In vivo toxicity was assessed using *Tenebrio molitor*, *Galleria mellonella*, and *Caenorhabditis elegans* models.
Main Results:
- PH265 and PH276 demonstrated broad-spectrum antifungal activity with MICs between 0.5–8 μg/mL against tested fungi.
- PH276 showed synergistic effects with fluconazole and caspofungin against *Candida haemulonii* (FIC ≤ 0.5).
- Both derivatives inhibited *Cryptococcus neoformans* biofilm formation and modulated polysaccharide capsule production, with no significant *in vivo* toxicity observed.
Conclusions:
- PH265 and PH276 are promising broad-spectrum antifungal agents with potential therapeutic applications.
- Their ability to disrupt biofilms and modulate fungal capsules, coupled with low toxicity, warrants further investigation.
- These compounds represent viable candidates for the development of new strategies against invasive fungal infections.
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