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用于催化抗癌治疗的锇(II)配合物:最新进展

Os(II) complexes for catalytic anticancer therapy: recent update.

作者信息

Kushwaha Rajesh, Kumar Ashish, Saha Souvik, Bajpai Sumit, Yadav Ashish Kumar, Banerjee Samya

机构信息

Department of Chemistry, Indian Institute of Technology (BHU), Varanasi, UP-221005, India.

出版信息

Chem Commun (Camb). 2022 Apr 14;58(31):4825-4836. doi: 10.1039/d2cc00341d.

Abstract

The recent dramatic enhancement in cancer-related mortality and the drawbacks (side effects and resistance) of Pt-based first-generation chemotherapeutics have escalated the need for new cancer medicines with unique anticancer activities for better human life. To overcome the demerits of Pt-based cancer drugs, the concept of catalytic anticancer agents has recently been presented in the field of anticancer metallodrug development research. Many intracellular transformations in cancer cells are catalyzed by metal complexes, including pyruvate reduction to lactate, NAD(P) reduction to NAD(P)H and , and the conversion of O to reactive oxygen species (ROS). These artificial in-cell changes with non-toxic and catalytic dosages of metal complexes have been shown to disrupt several essential intracellular processes which ultimately cause cell death. This new approach could develop potent next-generation catalytic anticancer drugs. In this context, recently, several 16/18 electron Os(II)-based complexes have shown promising catalytic anticancer activities with unique anticancer mechanisms. Herein, we have delineated the catalytic anticancer activity of Os(II) complexes from a critical viewpoint. These catalysts are reported to induce the in-cell catalytic transfer hydrogenation of pyruvate and important quinones to create metabolic disorder and photocatalytic ROS generation for oxidative stress generation in cancer cells. Overall, these Os(II) catalysts have the potential to be novel catalytic cancer drugs with new anticancer mechanisms.

摘要

近期,癌症相关死亡率急剧上升,第一代铂类化疗药物存在诸多弊端(副作用和耐药性),这使得人们对具有独特抗癌活性的新型抗癌药物的需求日益迫切,以改善人类生活。为克服铂类抗癌药物的缺点,催化抗癌剂的概念最近在抗癌金属药物开发研究领域中被提出。癌细胞中的许多细胞内转化过程由金属配合物催化,包括丙酮酸还原为乳酸、NAD(P)还原为NAD(P)H以及O转化为活性氧(ROS)。已证明,金属配合物以无毒且具有催化作用的剂量引发的这些人工细胞内变化会破坏几个关键的细胞内过程,最终导致细胞死亡。这种新方法有望开发出高效的下一代催化抗癌药物。在此背景下,最近,几种基于16/18电子Os(II)的配合物已显示出具有独特抗癌机制的、有前景的催化抗癌活性。在此,我们从关键角度阐述了Os(II)配合物的催化抗癌活性。据报道,这些催化剂可诱导癌细胞内丙酮酸和重要醌类的催化转移氢化反应,从而造成代谢紊乱,并通过光催化产生ROS以引发癌细胞内的氧化应激。总体而言,这些Os(II)催化剂有潜力成为具有新型抗癌机制的新型催化抗癌药物。

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