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

CORVI, MARIA M.; ROSSI, FRANCO; GANUZA, AGUSTINA; ALONSO, ANDRÉS M.; ALBERCA, LUCAS N.; DIETRICH, ROQUE C.; GAVERNET, LUCIANA; TALEVI, ALAN

PARASITOLOGY RESEARCH

SPRINGER

Año: 2023 vol. 123

0932-0113

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 to find 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, inthis study, we investigated the antiproliferative effect of several repurposed drugs. Of these, clofazimine and triclabendazoledisplayed a higher selectivity against T. gondii, affecting its replication. Furthermore, both compounds inhibited spermineincorporation into the parasite, which is necessary for the formation of other polyamines. The data reported here indicate thatclofazimine and triclabendazole could be used for the treatment of human toxoplasmosis and confirms that drug repurposingis an excellent strategy to find new therapeutic targets of intervention.