Speciation Studies of Monosubstituted Pt, Mo, and W Decavanadates in Culture Media and In Vitro Activity Against <i>Trypanosoma cruzi</i>

Polyoxovanadates (POVs) have been proposed as potential drugs against cancer and diabetes, as well as against viral and bacterial diseases. However, their potential application as bioactive compounds against trypanosomatid parasites remains unexplored. In this work, we evaluated for the first time the activity of decavanadate (V 10 ) and monosubstituted V 9 M structures with M = Pt(IV), Mo(VI), and W(VI) on Trypanosoma cruzi . In some cases, activity increased by 1–2 orders of magnitude compared to monomeric vanadate (EC 50 monomeric vanadate V 1 &gt; 1000 µM in epimastigotes and &gt;100 µM in trypomastigotes, EC 50 V 10 in epimastigotes = 1.5 µM, EC 50 V 9 Pt and V 9 Mo in trypomastigotes = 8.1 µM). Significant differences in activity were observed between the trypomastigote and epimastigote forms of the parasite. Cytotoxicity, evaluated in VERO cells, remained within the same order of magnitude for both decavanadate‐type structures and monomeric vanadate. 51 V NMR measurements performed in culture media showed that substitution significantly affects cluster stability and speciation. Metal uptake studies did not show differences that could explain the observed biological activity, and transcriptomic assays identified no significant impact at the gene expression level. These results are consistent with the interpretation that the effects occur at the proteomic level.