Long-chain 4-aminoquinolines inhibit filamentation and increase efficacy of nystatin against Candida albicans infections in vivo

  • NPJ Biofilms Microbiomes. 2024 Dec 13;10(1):146. doi: 10.1038/s41522-024-00608-3.
Aleksandar Pavic  1 ,  Natasa Radakovic  2 ,  Ivana Moric  2 ,  Nada Stankovic  2 ,  Dejan Opsenica  3  4 ,  Lidija Senerovic  2
Affiliations
  • 1. Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia. [email protected].
  • 2. Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
  • 3. Institute of Chemistry, Technology, and Metallurgy, University of Belgrade, Belgrade, Serbia.
  • 4. Centre of Excellence in Environmental Chemistry and Engineering, ICTM, Belgrade, Serbia.
PMID: 39672811 DOI: 10.1038/s41522-024-00608-3
Abstract

In exploring a growing demand for innovative approaches to tackle emerging and life threatening Fungal diseases, we identified long-chain 4-aminoquinoline (4-AQ) derivatives as a new class of anti-virulence agents. For the first time, we demonstrated that 4-AQs effectively prevent filamentation of Candida albicans, a key virulence trait, under multiple triggering conditions. Selected 4-AQ derivatives inhibited filament formation in a zebrafish model of disseminated candidiasis at 1.56 µM, with no toxicity up to 50 µM. Combining nystatin with 4-AQs resulted in a 100% survival rate of infected embryos and complete eradication of C. albicans, compared to 65-75% survival with nystatin alone. The most potent 4-AQ derivatives also showed significant activity against C. albicans biofilms, with derivative 11 suppressing mixed C. albicans-Pseudomonas aeruginosa biofilms. This dual capability highlights the potential of 4-AQs as novel anti-virulence agents to enhance conventional Antifungal therapies, marking a significant advance in treating complex Fungal infections.

Products