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Broth Microdilution In Vitro Screening: An Easy and Fast Method to Detect New Antifungal Compounds
Published on: February 14, 2018
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.
Abstract:
Occidiofungin, a glycolipopeptide obtained from the liquid culture of Burkholderia contaminans MS14, has been identified as a novel fungicide. The present study was designed to initially assess the in vitro toxicity in a rat hepatoma (H4IIE) cell line and acute toxicological effects of occidiofungin using a mouse model. In vitro toxicity was observed in all variables at 5 μmol/L. B6C3F1 mice were given single and repeat doses of occidiofungin up to 20 mg/kg. Key effects were a reduction in body and organ weights. However, no significant decrease in body weight was noted at a dose of 1 mg/kg, which is comparable to the dose level of other cyclic glycopeptide antifungal agents currently approved for human use. Microscopic examination of treated mice did not identify any signs of organ-specific toxicity at the dose levels tested.
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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