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金属配合物针对细胞内氧化还原平衡用于抗癌治疗

Targeting of the intracellular redox balance by metal complexes towards anticancer therapy.

作者信息

Murillo María Isabel, Gaiddon Christian, Le Lagadec Ronan

机构信息

Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México, Mexico.

Strasbourg Université, Inserm UMR_S U1113, IRFAC, Strasbourg, France.

出版信息

Front Chem. 2022 Aug 11;10:967337. doi: 10.3389/fchem.2022.967337. eCollection 2022.

Abstract

The development of cancers is often linked to the alteration of essential redox processes, and therefore, oxidoreductases involved in such mechanisms can be considered as attractive molecular targets for the development of new therapeutic strategies. On the other hand, for more than two decades, transition metals derivatives have been leading the research on drugs as alternatives to platinum-based treatments. The success of such compounds is particularly due to their attractive redox kinetics properties, favorable oxidation states, as well as routes of action different to interactions with DNA, in which redox interactions are crucial. For instance, the activity of oxidoreductases such as PHD2 (prolyl hydroxylase domain-containing protein) which can regulate angiogenesis in tumors, LDH (lactate dehydrogenase) related to glycolysis, and enzymes, such as catalases, SOD (superoxide dismutase), TRX (thioredoxin) or GSH (glutathione) involved in controlling oxidative stress, can be altered by metal effectors. In this review, we wish to discuss recent results on how transition metal complexes have been rationally designed to impact on redox processes, in search for effective and more specific cancer treatments.

摘要

癌症的发展通常与基本氧化还原过程的改变有关,因此,参与此类机制的氧化还原酶可被视为开发新治疗策略的有吸引力的分子靶点。另一方面,二十多年来,过渡金属衍生物一直引领着作为铂类治疗替代药物的研究。此类化合物的成功尤其归因于其具有吸引力的氧化还原动力学性质、有利的氧化态以及与DNA相互作用不同的作用途径,其中氧化还原相互作用至关重要。例如,诸如可调节肿瘤血管生成的PHD2(含脯氨酰羟化酶结构域蛋白)、与糖酵解相关的LDH(乳酸脱氢酶)以及参与控制氧化应激的过氧化氢酶、SOD(超氧化物歧化酶)、TRX(硫氧还蛋白)或GSH(谷胱甘肽)等氧化还原酶的活性可被金属效应物改变。在本综述中,我们希望讨论关于如何合理设计过渡金属配合物以影响氧化还原过程的最新研究结果,以寻找有效且更具特异性的癌症治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65eb/9405673/2c51ff73cdbf/fchem-10-967337-g001.jpg

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