A Novel Calcium-Dependent Protein Kinase 1 Inhibitor Potently Prevents Transmission to Foetuses in Mouse.

Treatments currently used to prevent congenital toxoplasmosis are non-specific of and have grievous side effects. To develop a more specific and less toxic drug, we have designed SP230, an imidazo[1,2-]pyridazine salt targeting the calcium-dependent protein kinase 1 (CDPK1) and active against acute toxoplasmosis in mice. Efficiency of SP230 to inhibit foetal transmission of the parasite was evaluated in a mouse model of congenital toxoplasmosis.

Imidazo[1,2-b]pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1 decrease the parasite burden in mice with acute toxoplasmosis.

The current therapeutic arsenal for toxoplasmosis is restricted to drugs non-specific to the parasite which cause important side effects. Development of more efficient and specific anti-Toxoplasma compounds is urgently needed. Imidazo[1,2-b]pyridazines designed to inhibit the calcium-dependent protein kinase 1 of Toxoplasma gondii (TgCDPK1) and effective against tachyzoite growth in vitro at submicromolar ranges were modified into hydrochloride salts to be administered in vivo in a mouse model of acute toxoplasmosis.

Enhancement of the protective efficacy of a ROP18 vaccine against chronic toxoplasmosis by nasal route.

Infection with the parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. No vaccine is currently available, so the design of efficient vaccine strategies is still a topical question. In this study, we evaluated the immunoprophylactic potential of a T.

The antigen-specific response to Toxoplasma gondii profilin, a TLR11/12 ligand, depends on its intrinsic adjuvant properties.

Agonists that activate Toll-like receptors (TLR) are potential vaccine adjuvants. In particular, Toxoplasma gondii profilin (TgPRF) is recognized by TLR11/12 to generate an inflammatory response. Unlike most TLR ligands, TgPRF is also a protein and can therefore simultaneously induce innate and adaptive immune responses.