Salmain Michèle, Gaschard Marie, Baroud Milad, Lepeltier Elise, Jaouen Gérard, Passirani Catherine, Vessières Anne
Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire (IPCM), 4 Place Jussieu, F-75005 Paris, France.
Micro & Nanomedecines Translationnelles (MINT), University of Angers, Inserm, The National Center for Scientific Research (CNRS), SFR ICAT, F-49000 Angers, France.
Cancers (Basel). 2023 Sep 6;15(18):4448. doi: 10.3390/cancers15184448.
Cancers classified as multidrug-resistant (MDR) are a family of diseases with poor prognosis despite access to increasingly sophisticated treatments. Several mechanisms explain these resistances involving both tumor cells and their microenvironment. It is now recognized that a multi-targeting approach offers a promising strategy to treat these MDR tumors. Inhibition of thioredoxin reductase (TrxR), a key enzyme in maintaining redox balance in cells, is a well-identified target for this approach. Auranofin was the first inorganic gold complex to be described as a powerful inhibitor of TrxR. In this review, we will first recall the main results obtained with this metallodrug. Then, we will focus on organometallic complexes reported as TrxR inhibitors. These include gold(I), gold(III) complexes and metallocifens, i.e., organometallic complexes of Fe and Os derived from tamoxifen. In these families of complexes, similarities and differences in the molecular mechanisms of TrxR inhibition will be highlighted. Finally, the possible relationship between TrxR inhibition and cytotoxicity will be discussed and put into perspective with their mode of action.
被归类为多药耐药（MDR）的癌症是一类疾病，尽管有越来越先进的治疗方法，但预后仍然很差。有几种机制可以解释这些耐药性，涉及肿瘤细胞及其微环境。现在人们认识到，多靶点方法为治疗这些MDR肿瘤提供了一种有前景的策略。抑制硫氧还蛋白还原酶（TrxR），一种维持细胞氧化还原平衡的关键酶，是这种方法中一个明确的靶点。金诺芬是第一个被描述为TrxR强效抑制剂的无机金配合物。在这篇综述中，我们将首先回顾用这种金属药物获得的主要结果。然后，我们将重点关注报道的作为TrxR抑制剂的有机金属配合物。这些包括金（I）、金（III）配合物和金属西芬，即源自他莫昔芬的铁和锇的有机金属配合物。在这些配合物家族中，将突出TrxR抑制分子机制的异同。最后，将讨论TrxR抑制与细胞毒性之间的可能关系，并根据它们的作用模式进行分析。
