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. 1992 Apr;36(4):779–782. doi: 10.1128/aac.36.4.779

Antimicrotubule benzimidazoles inhibit in vitro growth of Pneumocystis carinii.

M S Bartlett 1, T D Edlind 1, M M Durkin 1, M M Shaw 1, S F Queener 1, J W Smith 1
PMCID: PMC189407  PMID: 1503439

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bartlett M. S., Eichholtz R., Smith J. W. Antimicrobial susceptibility of Pneumocystis carinii in culture. Diagn Microbiol Infect Dis. 1985 Sep;3(5):381–387. doi: 10.1016/0732-8893(85)90076-8. [DOI] [PubMed] [Google Scholar]
  2. Bartlett M. S., Fishman J. A., Durkin M. M., Queener S. F., Smith J. W. Pneumocystis carinii: improved models to study efficacy of drugs for treatment or prophylaxis of Pneumocystis pneumonia in the rat (Rattus spp.). Exp Parasitol. 1990 Jan;70(1):100–106. doi: 10.1016/0014-4894(90)90089-u. [DOI] [PubMed] [Google Scholar]
  3. Bartlett M. S., Marr J. J., Queener S. F., Klein R. S., Smith J. W. Activity of inosine analogs against Pneumocystis carinii in culture. Antimicrob Agents Chemother. 1986 Jul;30(1):181–183. doi: 10.1128/aac.30.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bartlett M. S., Queener S. F., Tidwell R. R., Milhous W. K., Berman J. D., Ellis W. Y., Smith J. W. 8-Aminoquinolines from Walter Reed Army Institute for Research for treatment and prophylaxis of Pneumocystis pneumonia in rat models. Antimicrob Agents Chemother. 1991 Feb;35(2):277–282. doi: 10.1128/aac.35.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Black J. R., Feinberg J., Murphy R. L., Fass R. J., Carey J., Sattler F. R. Clindamycin and primaquine as primary treatment for mild and moderately severe Pneumocystis carinii pneumonia in patients with AIDS. Eur J Clin Microbiol Infect Dis. 1991 Mar;10(3):204–207. doi: 10.1007/BF01964465. [DOI] [PubMed] [Google Scholar]
  6. Edlind T. D., Hang T. L., Chakraborty P. R. Activity of the anthelmintic benzimidazoles against Giardia lamblia in vitro. J Infect Dis. 1990 Dec;162(6):1408–1411. doi: 10.1093/infdis/162.6.1408. [DOI] [PubMed] [Google Scholar]
  7. Hughes W. T., McNabb P. C., Makres T. D., Feldman S. Efficacy of trimethoprim and sulfamethoxazole in the prevention and treatment of Pneumocystis carinii pneumonitis. Antimicrob Agents Chemother. 1974 Mar;5(3):289–293. doi: 10.1128/aac.5.3.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hurtado M., Medina M. T., Sotelo J., Jung H. Sensitive high-performance liquid chromatographic assay for albendazole and its main metabolite albendazole sulphoxide in plasma and cerebrospinal fluid. J Chromatogr. 1989 Sep 29;494:403–407. doi: 10.1016/s0378-4347(00)82695-x. [DOI] [PubMed] [Google Scholar]
  9. Jaffe H. S., Abrams D. I., Ammann A. J., Lewis B. J., Golden J. A. Complications of co-trimoxazole in treatment of AIDS-associated Pneumocystis carinii pneumonia in homosexual men. Lancet. 1983 Nov 12;2(8359):1109–1111. doi: 10.1016/s0140-6736(83)90627-x. [DOI] [PubMed] [Google Scholar]
  10. Juliano C., Martinotti M. G., Cappuccinelli P. "In vitro" effect of microtubule inhibitors on Trichomonas vaginalis. Microbiologica. 1985 Jan;8(1):31–42. [PubMed] [Google Scholar]
  11. Jung H., Hurtado M., Medina M. T., Sanchez M., Sotelo J. Dexamethasone increases plasma levels of albendazole. J Neurol. 1990 Aug;237(5):279–280. doi: 10.1007/BF00314741. [DOI] [PubMed] [Google Scholar]
  12. Lacey E. The role of the cytoskeletal protein, tubulin, in the mode of action and mechanism of drug resistance to benzimidazoles. Int J Parasitol. 1988 Nov;18(7):885–936. doi: 10.1016/0020-7519(88)90175-0. [DOI] [PubMed] [Google Scholar]
  13. Michiels M., Hendriks R., Heykants J., van den Bossche H. The pharmacokinetics of mebendazole and flubendazole in animals and man. Arch Int Pharmacodyn Ther. 1982 Apr;256(2):180–191. [PubMed] [Google Scholar]
  14. Queener S. F., Bartlett M. S., Jay M. A., Durkin M. M., Smith J. W. Activity of lipid-soluble inhibitors of dihydrofolate reductase against Pneumocystis carinii in culture and in a rat model of infection. Antimicrob Agents Chemother. 1987 Sep;31(9):1323–1327. doi: 10.1128/aac.31.9.1323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Queener S. F., Bartlett M. S., Richardson J. D., Durkin M. M., Jay M. A., Smith J. W. Activity of clindamycin with primaquine against Pneumocystis carinii in vitro and in vivo. Antimicrob Agents Chemother. 1988 Jun;32(6):807–813. doi: 10.1128/aac.32.6.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Smith J. W., Bartlett M. S., Queener S. F., Durkin M. M., Jay M. A., Hull M. T., Klein R. S., Marr J. J. Pneumocystis carinii pneumonia therapy with 9-deazainosine in rats. Diagn Microbiol Infect Dis. 1987 Jun;7(2):113–118. doi: 10.1016/0732-8893(87)90028-9. [DOI] [PubMed] [Google Scholar]
  17. Toma E., Fournier S., Poisson M., Morisset R., Phaneuf D., Vega C. Clindamycin with primaquine for Pneumocystis carinii pneumonia. Lancet. 1989 May 13;1(8646):1046–1048. doi: 10.1016/s0140-6736(89)92446-x. [DOI] [PubMed] [Google Scholar]

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