Triclabendazole and clofazimine reduce replication and spermine uptake in vitro in Toxoplasma gondii

CORVI MARIA; ROSSI FRANCO; GANUZA AGUSTINA; ALONSO ANDRES; ALBERCA LUCAS NICOLAS; DIETRICH ROQUE CARLOS; GAVERNET LUCIANA; TALEVI ALAN

Parasitology Research

Springer Science and Business Media Deutschland GmbH

Año: 2023 vol. 123

Toxoplasmosis is a worldwide zoonosis caused by the protozoan parasite Toxoplasma gondii. Although this infection is generally asymptomatic in immunocompetent individuals, it can cause serious clinical manifestations in newborns with congenital infection or in immunocompromised patients. As current treatments are not always well tolerated, there is an urgent need tofnd new drugs against human toxoplasmosis. Drug repurposing has gained considerable momentum in the last decade and is a particularly attractive approach for the search of therapeutic alternatives to treat rare and neglected diseases. Thus, in this study, we investigated the antiproliferative efect of several repurposed drugs. Of these, clofazimine and triclabendazoledisplayed a higher selectivity against T. gondii, afecting its replication. Furthermore, both compounds inhibited spermine incorporation into the parasite, which is necessary for the formation of other polyamines. The data reported here indicate that clofazimine and triclabendazole could be used for the treatment of human toxoplasmosis and confrms that drug repurposing is an excellent strategy to fnd new therapeutic targets of intervention.