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Title:   Author  item
                                            FOMOVSKA, ALINA - University Of Chicagoitem
                                            WOOD, RICHARD - University Of Medicine And Dentistry Of New Jerseyitem
                                            MUI, ERNST - University Of Chicagoitem
                                            WELSH, WILLIAM - University Of Chicagoitem
                                            Dubey, Jitenderitem
                                            FERREIRA, LEANDRA - Collaboratoritem
                                            HICKMAN, MARK - Walter Reed Army Instituteitem
                                            LEE, PATRICIA - Walter Reed Army Instituteitem
                                            LEED, SUSAN - Walter Reed Army Instituteitem
                                            AUSCHWITZ, JENNIFER - Walter Reed Army Instituteitem
                                            SOMMERVILLE, CAROLINE - University Of Strathclydeitem
                                            WOODS, STUART - University Of Strathclydeitem
                                            ROBERTS, CRAIG - University Of Strathclydeitem
                                            MCLEOD, RIMA - University Of Chicago
  Submitted to: Journal of Medicinal Chemistry
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 10/30/2012
                                    Publication  Date: 12/1/2012
                                    Citation: Fomovska, A., Wood, R., Mui, E., Welsh, W., Dubey, J.P., Ferreira, L.R., Hickman, M., Lee, P., Leed, S., Auschwitz, J., Sommerville, C., Woods, S., Roberts, C., Mcleod, R. 2012. Salicylanilide inhibitors of Toxoplasma gondii. Journal of Medicinal Chemistry. 55:8375-8391.Interpretive Summary: Toxoplasma gondii is a single-celled parasite of all warm-blooded hosts worldwide.  It causes mental retardation and loss of vision in children, and abortion in livestock.  There is no effective, safe medicine to cure toxoplasmosis.  Here, the authors report a new group of chemicals that show promise to treat toxoplasmosis.  The results will be of interest to biologists, parasitologists, and public health workers.
                                Technical Abstract: Toxoplasma gondii (T. gondii) is an apicomplexan parasite that can cause eye disease, brain disease, and death, especially in congenitally infected and immunocompromised 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 anti-apicomplexan 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.


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