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Impact of Nitric Oxide-Release Kinetics on Antifungal Activity

Quincy E Grayton1, Ivie L Conlon1, Christopher A Broberg1

  • 1Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Journal of Fungi (Basel, Switzerland)
|May 24, 2024
PubMed

Insights

Nitric oxide (NO) demonstrates broad-spectrum antifungal activity against resistant fungi like Candida and Aspergillus. NO donors with faster release kinetics show enhanced efficacy and compatibility with existing antifungals.

Area of Science:

  • Antimicrobial drug discovery
  • Mycology
  • Medicinal chemistry

Background:

  • Rising drug resistance in pathogenic fungi poses a significant global health challenge.
  • Limited antifungal options and increasing multi-drug resistance contribute to higher healthcare costs and reduced patient quality of life.
  • Nitric oxide (NO) has shown antimicrobial potential, but its specific effects on fungal pathogens require further elucidation.

Purpose of the Study:

  • To investigate the broad-spectrum antifungal activity of nitric oxide (NO)-releasing small molecules.
  • To evaluate the impact of NO-release kinetics on antifungal efficacy against key pathogenic fungi.
  • To assess the compatibility of NO donors with existing antifungal therapies.

Main Methods:

  • Tested four nitric oxide-releasing small molecules against *Candida albicans*, *Candida auris*, *Cryptococcus neoformans*, and *Aspergillus fumigatus*.
  • Assessed antifungal effects after a 24-hour exposure to a bolus dose of NO.
  • Determined the relationship between NO donor half-life, effective concentration, and selectivity index.
  • Examined fungal surface morphology post-treatment.
  • Evaluated the synergistic potential of NO donors with conventional antifungals.

Main Results:

  • A single dose of NO eradicated tested fungal species within 24 hours.
  • NO donors with shorter half-lives demonstrated potent antifungal activity at lower concentrations, exhibiting wider selectivity indexes.
  • All tested NO donors induced significant surface destruction of fungal cells.
  • All NO donors showed compatibility with currently prescribed antifungal medications against various fungal species.

Conclusions:

  • Nitric oxide exhibits broad-spectrum efficacy against clinically relevant pathogenic fungi.
  • Controlled release kinetics of NO donors are crucial for optimizing antifungal potency and safety.
  • NO-releasing molecules represent a promising therapeutic strategy, potentially enhancing existing antifungal treatments.
Keywords:
Aspergillus fumigatusCandida albicansCandida aurisCryptococcus neoformansantifungalnitric oxide

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