Society for the Coordination of Therapeutic Researches, 20220 Algajola, France.
Institut Galien, Universite Paris-Saclay, 92296 Chatenay-Malabry, France.
Curr Pharm Des. 2019;25(31):3306-3322. doi: 10.2174/1381612825666190902161400.
Many rhenium (Re) complexes with potential anticancer properties have been synthesized in the recent years with the aim to overcome the clinical limitations of platinum agents. Re(I) tricarbonyl complexes are the most common but Re compounds with higher oxidation states have also been investigated, as well as hetero-metallic complexes and Re-loaded self-assembling devices. Many of these compounds display promising cytotoxic and phototoxic properties against malignant cells but all Re compounds are still at the stage of preclinical studies.
The present review focused on the rhenium based cancer drugs that were in preclinical and clinical trials were examined critically. The detailed targeted interactions and experimental evidences of Re compounds reported by the patentable and non-patentable research findings used to write this review.
In the present review, we described the most recent and promising rhenium compounds focusing on their potential mechanism of action including, phototoxicity, DNA binding, mitochondrial effects, oxidative stress regulation or enzyme inhibition. Many ligands have been described that modulating the lipophilicity, the luminescent properties, the cellular uptake, the biodistribution, and the cytotoxicity, the pharmacological and toxicological profile.
Re-based anticancer drugs can also be used in targeted therapies by coupling to a variety of biologically relevant targeting molecules. On the other hand, combination with conventional cytotoxic molecules, such as doxorubicin, allowed to take into profit the targeting properties of Re for example toward mitochondria. Through the example of the diseleno-Re complex, we showed that the main target could be the oxidative status, with a down-stream regulation of signaling pathways, and further on selective cell death of cancer cells versus normal cells.
近年来，为了克服铂类药物的临床局限性，已经合成了许多具有潜在抗癌特性的铼（Re）配合物。Re（I）三羰基配合物最为常见，但也研究了氧化态更高的 Re 化合物、杂金属配合物和 Re 负载的自组装器件。许多这些化合物对恶性细胞显示出有前景的细胞毒性和光毒性，但所有 Re 化合物仍处于临床前研究阶段。
本综述重点考察了处于临床前和临床试验阶段的基于 Re 的癌症药物。使用专利和非专利研究结果报告的 Re 化合物的详细靶向相互作用和实验证据用于编写本综述。
在本综述中，我们描述了最近和最有前途的 Re 化合物，重点介绍了它们潜在的作用机制，包括光毒性、DNA 结合、线粒体效应、氧化应激调节或酶抑制。已经描述了许多配体，这些配体调节亲脂性、发光特性、细胞摄取、生物分布和细胞毒性、药理学和毒理学特征。
基于 Re 的抗癌药物也可以通过与各种生物相关的靶向分子偶联用于靶向治疗。另一方面，与常规细胞毒性分子（如阿霉素）联合使用，使 Re 的靶向特性（例如针对线粒体）得以发挥作用。通过二硒代 Re 配合物的例子，我们表明主要靶标可能是氧化状态，随后是信号通路的下游调节，以及进一步的癌细胞与正常细胞的选择性细胞死亡。
