Treatment of murine pulmonary blastomycosis with SCH 39304, a new triazole antifungal agent.

Antimicrob Agents Chemother

Evans Memorial Department of Clinical Research, Boston University Medical Center, Massachusetts 02118.

Published: May 1990

SCH 39304, a broad-spectrum azole derivative, was evaluated in an experimental mouse model of blastomycosis pneumonia. Five days after being inoculated with Blastomyces dermatitidis, infected mice were treated with either oral SCH 39304, fluconazole, or intraperitoneal amphotericin B. A dose response protective effect was observed with SCH 39304 at 5 to 100 mg/kg of body weight per day, with 5 mg of SCH 39304 per kg per day providing activity similar to that of 100 mg of fluconazole per kg per day. Colony counts of yeasts in the lungs of mice sacrificed while on therapy with SCH 39304 were consistently below those of controls, and several lungs were sterile. We conclude that SCH 39304 is effective in murine blastomycosis treatment and deserves to be evaluated in the treatment of human blastomycosis.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC171713PMC
http://dx.doi.org/10.1128/AAC.34.5.896DOI Listing

Publication Analysis

Top Keywords

sch 39304
28
sch
7
0
7
treatment murine
4
murine pulmonary
4
blastomycosis
4
pulmonary blastomycosis
4
blastomycosis sch
4
39304 triazole
4
triazole antifungal
4

Similar Publications

Genaconazole (SCH 39304) is a potent triazole antifungal agent that is active both orally and topically. Genaconazole is a racemic mixture which contains 50% of the RR (SCH 42427) and 50% of the SS (SCH 42426) enantiomers. The RR isomer accounts for most of the antifungal activity of genaconazole.

View Article and Find Full Text PDF

Stereoselective interaction of the azole antifungal agent SCH39304 with the cytochrome P-450 monooxygenase system isolated from Cryptococcus neoformans.

Antimicrob Agents Chemother

July 1997

Department of Molecular Biology and Biotechnology, Krebs Institute for Biomolecular Research, Sheffield University, United Kingdom.

We investigated the stereoselective inhibition of growth and ergosterol biosynthesis by SCH39304 in the pathogenic fungus Cryptococcus neoformans obtained from four AIDS patients who failed fluconazole therapy and compared the results to those obtained with a wild-type strain. For all strains, the MICs of the RR isomer were approximately half those of the racemate, with the SS enantiomer showing no inhibitory activity. The 50% inhibitory concentrations for in vitro ergosterol biosynthesis correlated with the MIC data, indicating stereoselective inhibition of their target P-450 enzyme, sterol 14alpha-demethylase, as the cause of this difference.

View Article and Find Full Text PDF

Stereoselective interaction of SCH 39304, a triazole, with sterol 14alpha-demethylase of Aspergillus fumigatus.

J Antimicrob Chemother

May 1997

Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, The University of Sheffield, UK.

The inhibitory activity of SCH 39304 and its enantiomers on radial growth and on the target enzyme, sterol 14alpha-demethylase, in Aspergillus fumigatus was studied to assess the role of stereochemistry in the efficacy of the drug. SCH 39304 and the RR(+) enantiomer were active in inhibiting the growth while no inhibition in the growth was observed with the SS(-) enantiomer. The MIC of SCH 39304 for the growth was about twice that of the RR(+) enantiomer.

View Article and Find Full Text PDF

Differential inhibition of Candida albicans CYP51 with azole antifungal stereoisomers.

FEMS Microbiol Lett

April 1997

Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, UK.

Azole antifungal compounds are important in agriculture and in the treatment of mycotic infection. The target enzyme, sterol 14 alpha-demethylase (CYP51), is inhibited through binding of triazole N-4 to the haem of this P450, as a sixth ligand together with the N-1 substituent groups interacting in some way with the apoprotein. Here we use Saccharomyces cerevisiae expression systems for the target enzyme of Candida albicans to investigate binding of enantiomers of the azole antifungal compounds SCH39304 and tetraconazole.

View Article and Find Full Text PDF

Triazole analogues which contained alkylthio or alkylsulfonyl groups where synthesized as derivatives of antifungal SM-8668 and estimated for their in vitro and in vivo activity. Derivatives having pentylthio, heptylthio or nonylthio groups showed excellent efficacy against both candidiasis and aspergillosis. Introduction of a hydrophilic group at the end of their alkyl chain made their activity stronger.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!