Repurpusing Triclabendazole and Clofazimine as putative anti-toxoplasma compounds

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

Salta

Congreso; Joint LV Annual SAIB Meeting and XIV PABMB Congress; 2019

SAIB-PABMB

Toxoplasmosisis an infection caused by the parasite Toxoplasma gondii. Althoughhealthy individuals present few symptoms, the disease could have a high impactin immunocompromised individuals and in congenital infection, leading serioushealth problems. Although the combination of pyrimethamine and sulphonamides isstill very effective for treatment of toxoplasmosis, the use of these two drugsin immunocompromised individuals for long periods of time frequently leads toadverse reactions. As such, there is a need for alternative therapeuticoptions. Recently, by application of in silico drug repurposing it wasreported that cisapride (gastroprokinetic agent), cinnarizine (antihistamineused to treat travel sickness), clofazimine (antimycobacterial compound),triclabendazole (antihelminthic drug) and paroxetine (antidepressant) inhibitputrescine uptake in Trypanosoma cruzi. Given that T. gondii isauxotroph for polyamines, here we evaluated these compounds on T. gondiigrowth in vitro. All the tested compounds presented anti-toxoplasmiceffect. The calculated IC50 for paroxetine, cinnarizine andcisapride were 2.42 uM,3.12 uMand 4.72 uMrespectively. However, triclabendazole and clofazimine presented a higherselectivity towards T. gondii inhibition growth, with IC500.61 uMand 0.3 uM,and selectivity indexes of 15.67 and 10.3 respectively. Our results suggestthat target and drug repurposing are valid approaches for the study of putativeantiparasitic compounds, especially for neglected diseases.