ThermoFAD® and in silico evaluation of Trypanosoma cruzi Trypanothione reductase (TcTR) inhibition by thiazolidine-2,4-dione derivatives

Chagas disease, endemic to Latin America and caused by Trypanosoma cruzi , has spread to nonendemic regions worldwide due to globalization and migration. Currently, the treatment options for Chagas' disease are limited (two drugs approved) and with severe side effects. This led to a search for less toxic and more potent drugs exploring innovative targets, such as Trypanosoma cruzi Trypanothione Reductase (TcTR). In our study, we optimized the ThermoFAD® assay for TcTR, leading to the identification of a thiazolidine-2,4-dione derivative (specifically, 5-(3,4dichlorobenzylidene) thiazolidine-2,4-dione) that stabilizes TcTR. We also employed in silico methods, such as Docking and Molecular Dynamics, to gain a deeper understanding of the biological activity data of these compounds.