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Acridine Derivatives as Antifungal and Antivirulence Agents Against Candida albicans
Amra Yunus1, Oluwatosin Oluwaseun Faleye1, Jin-Hyung Lee1
1School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Abstract:
Candida albicans is a clinically important fungal pathogen capable of causing both superficial and systemic infections, particularly in immunocompromised individuals. A key factor contributing to its pathogenicity is its ability to form biofilms, structured microbial communities that confer significant resistance to conventional antifungal therapies. Addressing this challenge, we explored the antivirulence potential of acridine derivatives, a class of heterocyclic aromatic compounds known for their diverse biological activities, including antimicrobial, antitumor, and antiparasitic properties. In this study, a series of acridine derivatives was screened against C. albicans biofilms, revealing notable inhibitory activity and highlighting their potential as scaffolds for the development of novel antifungal agents. Among the tested compounds, acridine-4-carboxylic acid demonstrated the most promising activity, significantly inhibiting the biofilm formation at 10 µg/mL without affecting planktonic cell growth, and with a minimum inhibitory concentration (MIC) of 60 µg/mL. Furthermore, it attenuated filamentation and cell aggregation in a fluconazole-resistant C. albicans strain. Toxicity assessments using Caenorhabditis elegans and plant models supported its low-toxicity profile. These findings highlight the potential of acridine-based scaffolds, particularly acridine-4-carboxylic acid, as lead structures for the development of therapeutics targeting both fungal growth and biofilm formation in Candida albicans infections.
Insights
Acridine derivatives show promise in combating Candida albicans biofilms, a major cause of drug-resistant fungal infections. Acridine-4-carboxylic acid effectively inhibits biofilm formation and virulence factors with low toxicity.
Area of Science:
- Mycology
- Medicinal Chemistry
- Antimicrobial Research
Background:
- Candida albicans is a significant fungal pathogen causing infections, especially in immunocompromised individuals.
- Biofilm formation by C. albicans confers resistance to antifungal drugs, necessitating new therapeutic strategies.
- Acridine derivatives possess diverse biological activities, including antimicrobial properties.
Purpose of the Study:
- To investigate the antivirulence potential of acridine derivatives against Candida albicans biofilms.
- To identify novel acridine-based compounds for developing new antifungal agents.
Main Methods:
- Screening of acridine derivatives for inhibitory activity against C. albicans biofilms.
- Determination of minimum inhibitory concentration (MIC) and effects on planktonic growth.
- Assessment of effects on filamentation and cell aggregation in fluconazole-resistant strains.
- Toxicity evaluation using Caenorhabditis elegans and plant models.
Main Results:
- Acridine derivatives exhibited significant inhibitory activity against C. albicans biofilms.
- Acridine-4-carboxylic acid showed potent biofilm inhibition at 10 µg/mL without affecting planktonic cells.
- Acridine-4-carboxylic acid demonstrated a low toxicity profile in model organisms.
- The compound also attenuated virulence factors like filamentation and aggregation.
Conclusions:
- Acridine-based scaffolds, particularly acridine-4-carboxylic acid, are promising for developing novel therapeutics against Candida albicans.
- These compounds can target both fungal growth and biofilm formation, addressing a critical challenge in antifungal therapy.
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