Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design.
Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design.
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DOI：
10.1038/ncomms7582
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发表时间：
2015-03-20
影响因子：
16.6
通讯作者：
Sadler, Peter J.
中科院分区：
文献类型：
--
作者：
Soldevila-Barreda, Joan J.;Romero-Canelon, Isolda;Habtemariam, Abraha;Sadler, Peter J.
有机膦配合物是有机反应中有效的加氢催化剂。例如，Noyori型钌络合物通过从甲酸盐转移氢化物来催化酮的还原。在这里，我们表明这种催化反应可以在癌细胞中实现，为设计安全的金属抗癌药物提供了新的策略。钌（II）磺酰氨基亚乙基胺配合物对人卵巢癌细胞的活性在低无毒剂量的甲酸盐存在下增强高达50倍。辅酶NAD+在细胞中转化为NADH的程度取决于甲酸盐浓度。这种新的细胞死亡的还原应激机制不涉及细胞凋亡或线粒体膜电位的扰动。相比之下，铱催化剂通过氧化应激导致癌细胞死亡。因此，有机络合物具有调节癌细胞氧化还原状态的非凡能力。 有机膦配合物是有机反应中有效的加氢催化剂。在这里，作者首次报道了转移氢化催化可以在细胞内发生，并可用作一种新的抗癌策略。
Organometallic complexes are effective hydrogenation catalysts for organic reactions. For example, Noyori-type ruthenium complexes catalyse reduction of ketones by transfer of hydride from formate. Here we show that such catalytic reactions can be achieved in cancer cells, offering a new strategy for the design of safe metal-based anticancer drugs. The activity of ruthenium(II) sulfonamido ethyleneamine complexes towards human ovarian cancer cells is enhanced by up to 50 × in the presence of low non-toxic doses of formate. The extent of conversion of coenzyme NAD+ to NADH in cells is dependent on formate concentration. This novel reductive stress mechanism of cell death does not involve apoptosis or perturbation of mitochondrial membrane potentials. In contrast, iridium cyclopentadienyl catalysts cause cancer cell death by oxidative stress. Organometallic complexes therefore have an extraordinary ability to modulate the redox status of cancer cells. Organometallic complexes are effective hydrogenation catalysts for organic reactions. Here the authors report for the first time that transfer hydrogenation catalysis can take place inside the cell and could be used as a novel anticancer strategy.
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影响因子：
6.6
作者：
Jungwirth U;Kowol CR;Keppler BK;Hartinger CG;Berger W;Heffeter P
通讯作者：
Heffeter P
影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
16.6
作者：
Betanzos-Lara, Soledad;Liu, Zhe;Sadler, Peter J.
通讯作者：
Sadler, Peter J.
影响因子：
16.6
作者：
Filipovic, Milos R.;Koh, Alaric C. W.;Ivanovic-Burmazovic, Ivana
通讯作者：
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