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Antimicrobial Agents and Chemotherapy, September 1998, p. 2284-2289, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Two 2-Hydroxy-3-Alkyl-1,4-Naphthoquinones with In Vitro and In Vivo Activities against Toxoplasma gondii

Anis A. Khan,1,2 Mohamed Nasr,3 and Fausto G. Araujo1,*

Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, Palo Alto, California 943011; Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 208923; and Division of Infectious Disease and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Palo Alto, California 943052

Received 26 September 1997/Returned for modification 25 November 1997/Accepted 29 June 1998

Two 3-alkyl-substituted 2-hydroxy-1,4-naphthoquinones, NSC 113452 (NSC52) and NSC 113455 (NSC55), were evaluated for activity against Toxoplasma gondii in vitro and in murine models of acute toxoplasmosis. In vitro, both NSC52 and NSC55 significantly inhibited intracellular replication of T. gondii. In vivo, each compound was examined alone and in combination with other drugs currently used for treatment of human toxoplasmosis. Although none of the compounds protected mice against death when administered orally, both were significantly protective when administered intraperitoneally. In addition, a significant increase in survival was observed when suboptimal doses of each compound were used in combination with suboptimal doses of pyrimethamine or sulfadiazine. These results indicate that combinations of NSC52 or NSC55 with pyrimethamine or sulfadiazine have promising activity against T. gondii.

* Corresponding author. Mailing address: Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, 860 Bryant St., Palo Alto, CA 94301. Phone: (650) 326-8120. Fax: (650) 329-9853. E-mail: faraujo{at}PAMFRI.ORG.

Antimicrobial Agents and Chemotherapy, September 1998, p. 2284-2289, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.




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