Antiproliferative effect of Triclabendazole and Clofazimine on T. gondii growth, a repurposing approach

GANUZA, A; ALBERCA, LN; DIETRICH, RC; GAVERNET, L; TALEVI, A; CORVI, MM

Mar del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019- XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); 2019

SAIC

Toxoplasmosis is an infection caused by theparasite Toxoplasma gondii. Although healthy individuals present fewsymptoms, the disease could have a high impact in immunocompromised individualsand in congenital infection, leading serious health problems. Although thecombination of pyrimethamine with a sulfonamide is still very effective for treatmentof toxoplasmosis, the use of these two drugs in immunocompromised individuals forlong periods of time frequently leads to adverse reactions. As such, there is aneed for alternative therapeutic options. Recently, by application of insilico drug repurposing it was reported that cisapride (gastroprokineticagent), cinnarizine (antihistamine used to treat travel sickness), clofazimine(antimycobacterial compound), triclabendazole (antihelminthic drug) andparoxetine (antidepressant) inhibit putrescine uptake in Trypanosoma cruzi.Given that T. gondii is auxotroph for polyamines, here we evaluatedthese compounds on T. gondii growth in vitro. All the testedcompounds presented anti-toxoplasmic effect. The calculated IC50 forparoxetine, cinnarizine and cisapride were 2.42 microM, 3.12 microM and 4.72 microM respectively. However,triclabendazole and clofazimine presented a higher selectivity towards T.gondii inhibition growth: selectivity index of 15.67 and 10.3 respectively(IC50 0.61 microM for triclabendazole and 0.3 microM for clofazimine)without showing a cytotoxic effect on host-cells. Our results suggest that targetand drug repurposing are valid approaches for the study of putativeantiparasitic compounds, especially for neglected diseases.