Activity of the Histone Deacetylase Inhibitor FR235222 on Toxoplasma gondii: Inhibition of Stage Conversion of the Parasite Cyst Form and Study of New Derivative Compounds

摘要: Bradyzoite-to-tachyzoite conversion plays a role in the pathogenesis of recrudescence ocular toxoplasmosis and disease immunocompromised persons. The currently available medicines are ineffective on cysts fail to prevent reactivation latent toxoplasmosis. A previous study showed that histone deacetylase inhibitor FR235222 has dramatic effect tachyzoite growth induces tachyzoite-to-bradyzoite vitro. present shows can target vitro-converted bradyzoites. Moreover, compound is active ex vivo T. gondii cysts. Free bradyzoites isolated after lysis cell wall did not proliferate vitro when cyst was treated with FR235222. results imply this able cross cystic wall. Fluorescent labeling impairs capacity convert without damaging integrity. In inoculation formerly fails infect mice these were We used our structural knowledge its target, HDAC3, synthesize new derivative compounds. identified two molecules highly against tachyzoites. They harbor better selectivity index more suitable for future approach. These identify derivatives as lead compounds range therapeutics acute chronic