Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach

Abstract

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. Although healthy individuals present few symptoms, the disease could have a high impact in immunocompromised individuals and in congenital infection, leading to serious health problems. Although the combination of pyrimethamine with a sulfonamide is still very effective for treatment of toxoplasmosis, the use of these two drugs in immunocompromised individuals for long periods of time frequently leads to adverse reactions. As such, there is a need for alternative therapeutic options. Recently, by application of in silico drug repurposing it was reported that cisapride (gastroprokinetic agent), cinnarizine (antihistamine used to treat travel sickness), clofazimine (antimycobacterial compound), triclabendazole (antihelminthic drug) and paroxetine (antidepressant) inhibit putrescine uptake in Trypanosoma cruzi. Given that T. gondii is auxotroph for polyamines, here we evaluated these compounds on T. gondii growth in vitro. All the tested compounds presented anti-toxoplasmic effect. The calculated IC50 for paroxetine, cinnarizine and cisapride were 2.42, 3.12 and 4.72 μM, 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 μM for triclabendazole and 0.3 μM for clofazimine) without showing a cytotoxic effect on host-cells. Our results suggest that target and drug repurposing are valid approaches for the study of putative antiparasitic compounds, especially for neglected diseases.