Trypanocidal Effect of Isotretinoin through the Inhibition of Polyamine and Amino Acid Transporters in Trypanosoma cruzi

    March 2017 in “ PLoS neglected tropical diseases ”
    Chantal Reigada, Edward A. Valera-Vera, Melisa Sayé, Andrea Emilse Errasti, Carla Cristi Avila, Mariana R. Miranda, Claudio A. Pereira
    TLDR Isotretinoin shows promise as a treatment for Chagas disease by effectively inhibiting key transporters in the parasite.
    The study investigated isotretinoin, an FDA-approved acne medication, for its potential as a trypanocidal drug against Trypanosoma cruzi, the parasite responsible for Chagas disease. Isotretinoin was identified through virtual screening and in vitro assays as an effective inhibitor of the polyamine transporter TcPAT12 and other amino acid transporters in T. cruzi. It demonstrated strong inhibition of trypomastigote burst from infected cells with an IC50 of 130 nM, while being less effective on the epimastigote stage. The drug did not affect mammalian cell viability or plasma membrane permeability of the parasites. The mechanism of action involved nutrient starvation leading to autophagic and apoptotic processes. The findings suggested that isotretinoin could be a promising treatment for Chagas disease due to its multi-target inhibition and existing approval for human use.
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