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 (LH,H) was modified to obtain the compounds LR1,R2 (R1 = H, R2 = Me and R1 = R2 = Me), which were used in the syntheses of complexes of composition [ReBr(CO)3LR1,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)3LMe,Me] complex, all compounds are more active than the standard drug, benznidazole (Bzn), while [ReBr(CO)3LH,H] also exhibited a much higher selectivity index. In addition, the interaction of megazol and its ReI 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.