- Salicylanilide inhibitors of Toxoplasma gondii
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Toxoplasma gondii (T. gondii) is an apicomplexan parasite that can cause eye disease, brain disease, and death, especially in congenitally infected and immune-compromised people. Novel medicines effective against both active and latent forms of the parasite are greatly needed. The current study focused on the discovery of such medicines by exploring a family of potential inhibitors whose antiapicomplexan activity has not been previously reported. Initial screening efforts revealed that niclosamide, a drug approved for anthelmintic use, possessed promising activity in vitro against T. gondii. This observation inspired the evaluation of the activity of a series of salicylanilides and derivatives. Several inhibitors with activities in the nanomolar range with no appreciable in vitro toxicity to human cells were identified. An initial structure-activity relationship was explored. Four compounds were selected for evaluation in an in vivo model of infection, and two derivatives with potentially enhanced pharmacological parameters demonstrated the best activity profiles.
- Fomovska, Alina,Mui, Ernest,McLeod, Rima,Wood, Richard D.,Welsh, William J.,Dubey, Jitenter P.,Ferreira, Leandra R.,Hickman, Mark R.,Lee, Patricia J.,Leed, Susan E.,Auschwitz, Jennifer M.,Sommerville, Caroline,Woods, Stuart,Roberts, Craig
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p. 8375 - 8391,17
(2020/09/15)
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