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A Cyclam Salt as an Antifungal Agent: Interference with Candida spp. and Cryptococcus neoformans Mechanisms of

Fátima Cerqueira1,2,3, Rui Medeiros1,2,3, Inês Lopes3,4

  • 1FP-I3ID, FP-BHS, GIT-LoSa, University Fernando Pessoa, Praça 9 de Abril, 349, 4249-004 Porto, Portugal.

Antibiotics (Basel, Switzerland)
|March 27, 2024
PubMed

Insights

A novel cyclam salt effectively combats high-priority yeasts like Candida albicans and Cryptococcus neoformans by inhibiting key virulence factors. This compound targets biofilm formation and specific fungal mechanisms without causing antioxidant effects at inhibitory concentrations.

Area of Science:

  • Medical Mycology
  • Antimicrobial Chemistry

Background:

  • Fungal infections caused by yeasts such as *Candida albicans*, *Cryptococcus neoformans*, and *Candida krusei* pose a growing threat, with several species classified as high-priority by the World Health Organization (WHO).
  • Developing new antifungal agents targeting virulence mechanisms is crucial for combating resistant fungal pathogens.

Purpose of the Study:

  • To investigate the efficacy of the cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against WHO-priority yeasts.
  • To determine the compound's interference with fungal virulence factors, including biofilm production, dimorphic transition, melanin synthesis, and catalase activity.

Main Methods:

  • Minimal Inhibitory Concentration (MIC) determination.
  • Assessment of biofilm production, catalase activity, dimorphic transition (*C. albicans*), and melanin production (*C. neoformans*).
  • DPPH assay for antioxidant activity and Griess reaction for nitric oxide (NO) detection in RAW264.7 macrophages.

Main Results:

  • The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 demonstrated significant inhibition of biofilm production and catalase activity in the tested yeasts.
  • The compound interfered with *C. albicans* dimorphic transition and *C. neoformans* melanin production.
  • No antioxidant effect was observed at MIC values. While reducing NO production in macrophages, the compound exhibited significant cytotoxicity.

Conclusions:

  • The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 exhibits promising antifungal activity by targeting critical virulence mechanisms of high-priority yeasts.
  • Further research is warranted to explore its therapeutic potential, considering the observed cytotoxicity in macrophage models.
Keywords:
Candida spp.Cryptococcus neoformansbiofilmscyclam saltvirulence mechanismsyeasts

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