TY - JOUR
T1 - A thiazole derivative of artemisinin moderately reduces toxoplasma gondii cyst burden in infected mice
AU - Schultz, Tracey L.
AU - Hencken, Christopher P.
AU - Woodard, Lauren E.
AU - Posner, Gary H.
AU - Yolken, Robert H.
AU - Jones-Brando, Lorraine
AU - Carruthers, Vern B.
PY - 2014
Y1 - 2014
N2 - Toxoplasmosis continues to be a public health problem, causing significant morbidity worldwide. Currently available medications, effective for acute toxoplasmosis, are nonetheless problematic due to adverse side effects in many patients. In addition, no medication is able to completely eradicate the parasite cysts, rendering infected individuals at risk for reactivation upon becoming immunocompromised. We examined the anti-T. gondii activity of 2 derivatives of artemisinin. In vitro metabolic stability tests revealed that both derivatives are stable in mouse plasma but only the thiazole CPH4-136 is stable in the presence of mouse microsomes. When tested in a mouse model of acute toxoplasmosis, both derivatives showed modest efficacy dependent upon the compound dose and the solvent vehicle. Finally, in a mouse model of chronic T. gondii infection, CPH4-136 at 3 mg/kg once per day for 32 days moderately but significantly decreased mouse brain cyst burden. Collectively, our findings suggest that artemisinin derivatives are partially effective in treating experimental T. gondii infections.
AB - Toxoplasmosis continues to be a public health problem, causing significant morbidity worldwide. Currently available medications, effective for acute toxoplasmosis, are nonetheless problematic due to adverse side effects in many patients. In addition, no medication is able to completely eradicate the parasite cysts, rendering infected individuals at risk for reactivation upon becoming immunocompromised. We examined the anti-T. gondii activity of 2 derivatives of artemisinin. In vitro metabolic stability tests revealed that both derivatives are stable in mouse plasma but only the thiazole CPH4-136 is stable in the presence of mouse microsomes. When tested in a mouse model of acute toxoplasmosis, both derivatives showed modest efficacy dependent upon the compound dose and the solvent vehicle. Finally, in a mouse model of chronic T. gondii infection, CPH4-136 at 3 mg/kg once per day for 32 days moderately but significantly decreased mouse brain cyst burden. Collectively, our findings suggest that artemisinin derivatives are partially effective in treating experimental T. gondii infections.
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U2 - 10.1645/13-451.1
DO - 10.1645/13-451.1
M3 - Article
C2 - 24524228
AN - SCOPUS:84907351386
SN - 0022-3395
VL - 100
SP - 516
EP - 521
JO - Journal of Parasitology
JF - Journal of Parasitology
IS - 4
ER -