Data Sheet 1_Metal-based compounds and Chagas disease treatment: current knowledge and therapeutic perspectives.pdf

Chagas disease (CD) is a parasitic infection caused by the protozoan Trypanosoma cruzi. CD treatment is restricted to benznidazole (BZN) and nifurtimox, with the former being the treatment of choice in many countries. Unfortunately, BZN demonstrates limited efficacy in the chronic phase of CD and leads to several side effects that often result in patients discontinuing the treatment. The emergence of BZN-resistant T. cruzi strains is also a major concern. Metal compounds have gained importance due to their unique physicochemical properties. Therefore, we conducted a 5-year systematic review, analysing 22 articles with the aim of compiling the results of the anti-trypanocidal effect of 113 compounds. Our results show that the majority of the compounds centre on Cu (17%), followed by Zn (12%) and Sn (9%). Most exhibit an anti-T. cruzi effect across all life-cycle forms, with epimastigotes generally being more resistant than trypomastigotes. Only 43 compounds (38%) had their mode of action elucidated, which included disruption of mitochondrial membrane potential, an increase in reactive oxygen species generation, and inhibition of ergosterol synthesis, cruzain, trypanothione reductase, and fumarate reductase. Despite our inability to establish the most effective metal compound due to a lack of standardisation in the methods used, this review seeks to outline a path for the design of new metallodrugs, a class of compounds that warrants further investigation for its promising anti-T. cruzi activity.