Paper
In vitro effects of three new 1,2,4-trioxanes (pentatroxane, thiahexatroxane, and hexatroxanone) on Toxoplasma gondii
Published Oct 1, 1989 · H. R. Chang, C. W. Jefford, J. Pechère
Antimicrobial Agents and Chemotherapy
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Abstract
The in vitro effects of three synthetic, cis-fused, bicyclic 1,2,4-trioxanes (pentatroxane, thiahexatroxane, and hexatroxanone) against intracellular Toxoplasma gondii were studied. Unactivated peritoneal macrophages were infected with the virulent RH strain of T. gondii and exposed to the 1,2,4-trioxanes at different concentrations. The antitoxoplasmic activity of the drugs was first assessed with [3H]uracil, which is incorporated by the parasite but not the host cell. Pentatroxane and thiahexatroxane were the most active, exhibiting 90% inhibitory concentrations of 6.8 and 5.3 micrograms/ml, respectively. Furthermore, microscopic examination of the infected macrophages after treatment with pentatroxane, thiahexatroxane, and hexatroxanone at their respective 90% inhibitory concentrations confirmed the inhibition of intracellular growth of T. gondii. Their activities were comparable to those of pyrimethamine (1 micrograms/ml) and pyrimethamine (0.1 micrograms/ml) in combination with sulfadiazine (25 micrograms/ml). Pentatroxane and thiahexatroxane were also able to inhibit intracellular growth of T. gondii within nonprofessional phagocytes (HeLa cells), suggesting that the antitoxoplasmic activity was not caused by a macrophage-specific mechanism, such as macrophage activation. However, the 1,2,4-trioxanes were not active against extracellular T. gondii. Pentatroxane and thiahexatroxane are new, promising compounds that deserve further study to assess their usefulness for treating toxoplasmosis.
Pentatroxane and thiahexatroxane show promising antitoxoplasmic activity, suggesting potential for treating toxoplasmosis.
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