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钌(II)-芳基配合物的抗肿瘤活性和催化潜力及其 N,O-供体配体

Anticancer Activity and Catalytic Potential of Ruthenium(II)-Arene Complexes with N,O-Donor Ligands.

机构信息

INRS-Institut Armand-Frappier , Université du Québec , 531 boul. des Prairies , Laval , Quebec H7V 1B7 , Canada.

出版信息

Inorg Chem. 2018 Jul 2;57(13):7558-7567. doi: 10.1021/acs.inorgchem.8b00346. Epub 2018 Jun 11.

DOI:10.1021/acs.inorgchem.8b00346
PMID:29888595
Abstract

The special ability of organometallic complexes to catalyze various transformations might offer new effective mechanisms for the treatment of cancer. Studies that report both the biological properties and the ability of metallic complexes to promote therapeutically relevant catalytic reactions are limited. Herein, we report the anticancer activity and catalytic potential of some ruthenium(II)-arene complexes bearing bidentate Schiff base ligands (2a and 2b) and their reduced analogues (5a and 5b, respectively). In comparison to their Schiff base counterparts 2a and 2b, we demonstrate that amine complexes 5a and 5b display (i) a higher in vitro antiproliferative activity on different human cancer cell lines, (ii) a lower rate of hydrolysis, and (iii) an improved initial catalytic rate for the reduction of NAD to NADH. In contrast to their imine analogues 2a and 2b, we also show that amine complexes 5a and 5b induce the generation of intracellular reactive oxygen species (ROS) in MCF-7 breast cancer cells. Our results highlight the impact that a simple ligand modification such as the reduction of an imine moiety can have on both the catalytic and biological activities of metal complexes. Moreover, the ruthenium complexes reported here display some antiproliferative activity against T47D breast cancer cells, known for their cis-platin resistance.

摘要

金属有机配合物催化各种转化的特殊能力可能为癌症治疗提供新的有效机制。报道生物性质和金属配合物促进治疗相关催化反应能力的研究是有限的。本文报道了一些钌(II)-芳基配合物的抗癌活性和催化潜力,这些配合物带有双齿席夫碱配体(2a 和 2b)及其还原类似物(5a 和 5b,分别)。与它们的席夫碱对应物 2a 和 2b 相比,我们证明了胺配合物 5a 和 5b 具有(i)对不同人癌细胞系更高的体外增殖活性,(ii)更低的水解速率,以及(iii)对 NAD 还原为 NADH 的初始催化速率提高。与它们的亚胺类似物 2a 和 2b 相比,我们还表明,胺配合物 5a 和 5b 在 MCF-7 乳腺癌细胞中诱导细胞内活性氧(ROS)的产生。我们的结果强调了简单的配体修饰(如亚胺部分的还原)对金属配合物的催化和生物活性的影响。此外,本文报道的钌配合物对 T47D 乳腺癌细胞(以其顺铂耐药性而闻名)具有一定的增殖活性。

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