Rhenium(I) and technetium(I) complexes with megazol derivatives: towards the development of a theranostic platform for Chagas disease

The diagnosis and treatment of Chagas disease (CD) in the chronic phase remains a challenge. With that in mind, a potential theranostic device based on the trypanocidal agent known as megazol and the -M(CO) (M = Re or Tc) fragment is proposed in the present work. The peripheral structure of megazol (L ) was modified to obtain the compounds L (R1 = H, R2 = Me and R1 = R2 = Me), which were used in the syntheses of complexes of composition [ReBr(CO) L ]. These compounds were studied by elemental analysis, FTIR, UV-vis, NMR ( H and C), HR-ESI-MS, HPLC/UPLC and single-crystal XRD. The trypanocidal activity of the rhenium complexes was evaluated against the intracellular form of . With exception of the [ReBr(CO) L ] complex, all compounds are more active than the standard drug, benznidazole (Bzn), while [ReBr(CO) L ] also exhibited a much higher selectivity index. In addition, the interaction of megazol and its Re complex was evaluated with the Old Yellow Enzyme (TcOYE) by both experimental and computational methods. The data showed that megazol as well as its metal complex exhibited a higher affinity for TcOYE compared to Bzn. Finally, the labelling of megazol with Tc was successfully carried out. However, the results indicated that the Re complexes used as standards were not homologous with the Tc complexes. Despite this discrepancy, this research suggests that the investigation into Re and Tc complexes with megazol could lead to the development of a theranostic device for CD in a near future.