Identification of new Trypanosoma cruzi-specific protein synthesis inhibitors by using a developed high-throughput in vitro translation assay

by Mantovani CC, Freitas FRN, Moraes CB, Dos Santos GRR, Cruz LR, Kratz JM, Aktas BH, Schenkman S. International Journal for Parasitology: Drugs and Drug Resistance 2026:32:100667. doi:10.1016/j.ijpddr.2026.100667

Summary: Since there are significant differences between the protein synthesis machinery of Trypanosoma cruzi, the causative agent of Chagas disease, and that of humans, it is likely that T. cruzi-specific protein synthesis inhibitors could be employed for the treatment of Chagas disease. The authors of this manuscript demonstrated that extracts derived from a T. cruzi strain deficient for hemin accumulation could be used to screen chemical libraries in a first-of-its-kind T. cruzi in vitro translation system. They optimized assay conditions, adapted them to a 384-well format, and miniaturized this assay to a 5 μL volume for use in ultra-high throughput screening. In a proof-of-principle pilot study, they identified quinazoline compounds that inhibit translation of reporter mRNAs by T. cruzi extracts.

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