Baek K-H, Lee H, Byun S, Genilloud O, Ioset J-R, Shum D, No JH. International Journal for Parasitology: Drugs and Drug Resistance 2026,31:100651. doi: 10.1016/j.ijpddr.2026.100651
Summary: Thus far, most drug discovery efforts for Chagas disease, caused by Trypanosoma cruzi, have relied upon cell-based assays. The failure of posaconazole in clinical trials has highlighted the need for more sophisticated characterization of phenotypically identified T. cruzi inhibitors. The authors of this manuscript evaluated 2,422 compounds against intracellular T. cruzi amastigotes and identified thirty growth inhibitors, including five serotonin-dopamine receptor antagonists and seven TGF-β receptor inhibitors. Fast-acting compounds inhibited intracellular amastigote proliferation within 48 h of incubation, while slow-acting compounds required prolonged exposure. Six inhibitors displayed potent inhibitory activity against all three parasite life-cycle stages. Finally, parasite painting was used to classify compounds based on morphological perturbations. The assays used in this study can faciliate prioritization of inhibitors for further development.
