Antimicrotubule benzimidazoles inhibit in vitro growth of Pneumocystis carinii

Author:

Bartlett M S1,Edlind T D1,Durkin M M1,Shaw M M1,Queener S F1,Smith J W1

Affiliation:

1. Indiana University School of Medicine, Indianapolis 46202-5250.

Abstract

Nine antimicrotubule benzimidazole derivatives tested in a Pneumocystis carinii culture system with human embryonic lung fibroblast monolayers inhibited organism proliferation. The concentrations of drugs inhibitory in culture ranged from 10 to 0.1 micrograms/ml, with thiabendazole being the least effective (10 micrograms/ml) and parbendazole being the most effective (0.1 microgram/ml). The parent compound, benzimidazole, was inactive at 10 micrograms/ml. Demonstration that this group of compounds has activity against P. carinii provides a new potential target that can be exploited, the microtubules. Also, the variability in the effectiveness of the compounds provides the basis for studies of structure-activity relationships, which were initiated in this study.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference20 articles.

1. Antimicrobial susceptibility of Pneumocystis carinii in culture;Bartlett M. S.;Diagn. Microbiol. Infect. Dis.,1985

2. Pneumocystis cainni: improved models to study efficacy of drugs for treatment or prophylaxis of Pneumocystis carinii in the rat (Rattus sp);Bartlett M. S.;Exp. Parasitol.,1990

3. Activity of inosine analogs against Pneumocystis carinii in culture;Bartlett M. S.;Antimicrob. Agents Chemother.,1986

4. Bartlett M. S. S. F. Queener and J. W. Smith. 1990. Imidazole antifungal drugs are ineffective therapy against Pneumocystis pneumonia in rats abstr. 138 p. 177. Abstr. Int. Congr. Infect. Dis. Montreal Quebec Canada.

5. 8-Aminoquinolines from Walter Reed Army Institute for Research for treatment and prophylaxis of Pneumocystis pneumonia in rat models;Bartlett M. S.;Antimicrob. Agents Chemother.,1991

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