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.

中文翻译：

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铼 （I） 和锝 （I） 配合物与兆唑衍生物：迈向美洲锥虫病治疗诊断学平台的开发


慢性期恰加斯病 （CD） 的诊断和治疗仍然是一个挑战。考虑到这一点，本研究提出了一种基于称为 megazol 的锥虫杀灭剂和 fac-M（CO）₃⁺（M = Re 或 ^99mTc）片段的潜在治疗诊断装置。修饰 megazol （L^H，H） 的外周结构以获得化合物 L^R1，R2 （R1 = H， R2 = Me 和 R1 = R2 = Me），这些化合物用于合成组成物 [ReBr（CO）₃L^R1，R2] 的复合物。通过元素分析、FTIR、UV-vis、NMR（¹H 和 ¹³C）、HR-ESI-MS、HPLC/UPLC 和单晶 XRD 研究了这些化合物。在体外评估铼复合物的锥虫杀灭活性与细胞内形式的克氏锥虫。除 [ReBr（CO）₃L^Me，Me] 复合物外，所有化合物都比标准药物苄硝唑 （Bzn） 更具活性，而 [ReBr（CO）₃L^H，H] 也表现出高得多的选择性指数。此外，通过实验和计算方法评估了 megazol 及其 Re 复合物与 T. cruzi Old Yellow Enzyme （TcOYE） 的相互作用。数据显示，与 Bzn 相比，megazol 及其金属络合物对 TcOYE 表现出更高的亲和力。最后，成功进行了 ^99mTc 的 megazol 标记。然而，结果表明，用作标准的 Re 复合物与 ^99mTc 复合物不是同源的。 尽管存在这种差异，但这项研究表明，对 Re 和 ^99mTc 配合物与 megazol 的研究可能会导致在不久的将来开发用于 CD 的治疗诊断装置。