Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1990 Feb;34(2):225–228. doi: 10.1128/aac.34.2.225

Efficacy of a hydroxynaphthoquinone, 566C80, in experimental Pneumocystis carinii pneumonitis.

W T Hughes 1, V L Gray 1, W E Gutteridge 1, V S Latter 1, M Pudney 1
PMCID: PMC171561  PMID: 2327770

Abstract

The efficacy of a new class of drugs for Pneumocystis carinii pneumonitis was demonstrated. 566C80, a hydroxynaphthoquinone, administered orally in a dose of greater than or equal to 100 mg/kg of body weight per day prophylactically prevented P. carinii pneumonitis in 90% or more of rats, while all untreated control animals developed pneumonitis. When 566C80 (100 mg/kg per day) was administered for 3 weeks after P. carinii pneumonitis was established, therapy was totally effective and all of the untreated controls had progressive P. carinii pneumonitis. A dose of 566C80 of between 25 and 50 mg/kg per day protected 50% of the rats from P. carinii pneumonitis, and a dose of between 50 and 100 mg/kg per day cured 50% of those treated for P. carinii pneumonitis. Both prophylaxis and treatment with 566C80 were at least as effective as with trimethoprim-sulfamethoxazole. Animals maintained on immunosuppression after completion of treatment remained free of P. carinii, suggesting a killing effect. Clearance of P. carinii was associated with levels of 60 micrograms or more of 566C80 per ml of plasma. This hydroxynaphthoquinone offers promise as an anti-P. carinii drug.

Full text

PDF

Selected References

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

  1. Boveris A., Stoppani A. O., Docampo R., Cruz F. S. Superoxide anion production and trypanocidal action of naphthoquinones on Trypanosoma cruzi. Comp Biochem Physiol C. 1978;61 100(2):327–329. doi: 10.1016/0306-4492(78)90063-1. [DOI] [PubMed] [Google Scholar]
  2. Docampo R., Cruz F. S., Boveris A., Muniz R. P., Esquivel D. M. Lipid peroxidation and the generation of free radicals, superoxide anion, and hydrogen peroxide in beta-lapachone-treated Trypanosoma cruzi epimastigotes. Arch Biochem Biophys. 1978 Mar;186(2):292–297. doi: 10.1016/0003-9861(78)90438-1. [DOI] [PubMed] [Google Scholar]
  3. Fieser L. F., Schirmer J. P., Archer S., Lorenz R. R., Pfaffenbach P. I. Naphthoquinone antimalarials. XXIX. 2-hydroxy-3-(omega-cyclohexylalkyl)-1,4-naphthoquinones. J Med Chem. 1967 Jul;10(4):513–517. doi: 10.1021/jm00316a001. [DOI] [PubMed] [Google Scholar]
  4. Fry M., Hudson A. T., Randall A. W., Williams R. B. Potent and selective hydroxynaphthoquinone inhibitors of mitochondrial electron transport in Eimeria tenella (Apicomplexa: Coccidia). Biochem Pharmacol. 1984 Jul 1;33(13):2115–2122. doi: 10.1016/0006-2952(84)90581-1. [DOI] [PubMed] [Google Scholar]
  5. Hudson A. T., Randall A. W., Fry M., Ginger C. D., Hill B., Latter V. S., McHardy N., Williams R. B. Novel anti-malarial hydroxynaphthoquinones with potent broad spectrum anti-protozoal activity. Parasitology. 1985 Feb;90(Pt 1):45–55. doi: 10.1017/s0031182000049003. [DOI] [PubMed] [Google Scholar]
  6. Hughes W. T., Kuhn S., Chaudhary S., Feldman S., Verzosa M., Aur R. J., Pratt C., George S. L. Successful chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med. 1977 Dec 29;297(26):1419–1426. doi: 10.1056/NEJM197712292972602. [DOI] [PubMed] [Google Scholar]
  7. Hughes W. T. Limited effect of trimethoprim-sulfamethoxazole prophylaxis on Pneumocystis carinii. Antimicrob Agents Chemother. 1979 Sep;16(3):333–335. doi: 10.1128/aac.16.3.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Lopes J. N., Cruz F. S., Docampo R., Vasconcellos M. E., Sampaio M. C., Pinto A. V., Gilbert B. In vitro and in vivo evaluation of the toxicity of 1,4-naphthoquinone and 1,2-naphthoquinone derivatives against Trypanosoma cruzi. Ann Trop Med Parasitol. 1978 Dec;72(6):523–531. doi: 10.1080/00034983.1978.11719356. [DOI] [PubMed] [Google Scholar]
  10. McHardy N., Haigh A. J., Dolan T. T. Chemotherapy of Theileria parva infection. Nature. 1976 Jun 24;261(5562):698–699. doi: 10.1038/261698a0. [DOI] [PubMed] [Google Scholar]
  11. Meshnick S. R., Blobstein S. H., Grady R. W., Cerami A. An approach to the development of new drugs for African trypanosomiasis. J Exp Med. 1978 Aug 1;148(2):569–579. doi: 10.1084/jem.148.2.569. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES