Activity of phenothiazines against medically important yeasts

Area of Science:

• Mycology
• Pharmacology
• Infectious Diseases

Background:

• Pathogenic yeasts like Candida albicans and Cryptococcus neoformans cause serious infections.
• Antifungal drug development is crucial for treating invasive fungal diseases.
• Phenothiazines are known for their antipsychotic properties but may have other biological activities.

Purpose of the Study:

• To investigate the in vitro antifungal activity of phenothiazine compounds trifluoperazine and chlorpromazine.
• To evaluate the in vivo efficacy of trifluoperazine against experimental yeast infections.
• To explore the potential of these drugs for treating fungal meningitis.

Main Methods:

• Minimum Inhibitory Concentrations (MICs) were determined for trifluoperazine and chlorpromazine against five common pathogenic yeasts.
• Mice were infected with Candida albicans or Cryptococcus neoformans and treated with daily intraperitoneal injections of trifluoperazine.
• Survival rates of treated and control mice were compared.

Main Results:

• Both trifluoperazine and chlorpromazine inhibited yeast growth in vitro, with MICs between 10 and 40 µg/ml.
• Daily trifluoperazine injections (4–7 mg/kg) significantly increased the survival of mice infected with Candida albicans.
• Trifluoperazine treatment also improved survival in mice infected with Cryptococcus neoformans.

Conclusions:

• Phenothiazine compounds exhibit significant antifungal activity against common pathogenic yeasts.
• Trifluoperazine demonstrates therapeutic potential in vivo for treating infections caused by Candida albicans and Cryptococcus neoformans.
• These findings suggest a potential role for trifluoperazine and related compounds in managing fungal meningitis.