Development of Toxoplasma gondiiCalcium-DependentProtein Kinase 1 (TgCDPK1) Inhibitors with PotentAnti-ToxoplasmaActivity.

Toxoplasmosis is a disease of prominent health concernthat iscaused by the protozoan parasite Toxoplasma gondii. Proliferation of T. gondiiis dependent on itsability to invade host cells, which is mediated in part by calcium-dependentprotein kinase 1 (CDPK1). We have developed ATP competitive inhibitorsof TgCDPK1 that block invasion of parasites intohost cells, preventing their proliferation. The presence of a uniqueglycine gatekeeper residue in TgCDPK1 permits selectiveinhibition of the parasite enzyme over human kinases. These potent TgCDPK1 inhibitors do not inhibit the growth of human celllines and represent promising candidates as toxoplasmosis therapeutics. [ABSTRACT FROM AUTHOR]