Nonclinical toxicological evaluation of occidiofungin, a unique glycolipopeptide antifungal

Wei Tan1, Jim Cooley, Frank Austin

  • 1Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.

Insights

Occidiofungin, a novel fungicide, showed in vitro toxicity at 5 μmol/L. In mice, doses up to 20 mg/kg caused weight reduction, but 1 mg/kg was safe, indicating potential for antifungal drug development.

Area of Science:

  • Microbiology
  • Toxicology
  • Pharmacology

Background:

  • Occidiofungin is a novel glycolipopeptide fungicide derived from Burkholderia contaminans MS14.
  • Cyclic glycopeptide antifungals are used in human medicine.

Purpose of the Study:

  • To assess the in vitro toxicity of occidiofungin in a rat hepatoma cell line (H4IIE).
  • To evaluate the acute toxicological effects of occidiofungin in a mouse model.

Main Methods:

  • In vitro toxicity testing using H4IIE cells.
  • Acute and repeat-dose toxicity studies in B6C3F1 mice with doses up to 20 mg/kg.

Main Results:

  • In vitro toxicity observed at 5 μmol/L.
  • Doses up to 20 mg/kg in mice led to reduced body and organ weights.
  • No significant body weight decrease or organ-specific toxicity at 1 mg/kg dose.

Conclusions:

  • Occidiofungin exhibits in vitro toxicity at 5 μmol/L.
  • A dose of 1 mg/kg in mice is comparable to therapeutic levels of approved antifungals, showing no significant adverse effects.
  • Occidiofungin demonstrates a potential safety profile for further development as an antifungal agent.

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