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

Abstract

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 fac-M(CO)₃⁺ (M = Re or ^99mTc) fragment is proposed in the present work. The peripheral structure of megazol (L^H,H) was modified to obtain the compounds L^R1,R2 (R1 = H, R2 = Me and R1 = R2 = Me), which were used in the syntheses of complexes of composition [ReBr(CO)₃L^R1,R2]. These compounds were studied by elemental analysis, FTIR, UV-vis, NMR (¹H and ¹³C), HR-ESI-MS, HPLC/UPLC and single-crystal XRD. The trypanocidal activity of the rhenium complexes was evaluated in vitro against the intracellular form of Trypanosoma cruzi. With exception of the [ReBr(CO)₃L^Me,Me] complex, all compounds are more active than the standard drug, benznidazole (Bzn), while [ReBr(CO)₃L^H,H] also exhibited a much higher selectivity index. In addition, the interaction of megazol and its Re^I complex was evaluated with the T. cruzi 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 ^99mTc was successfully carried out. However, the results indicated that the Re complexes used as standards were not homologous with the ^99mTc complexes. Despite this discrepancy, this research suggests that the investigation into Re and ^99mTc complexes with megazol could lead to the development of a theranostic device for CD in a near future.