School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013 PR China.
Inorg Chem. 2011 Aug 1;50(15):6929-37. doi: 10.1021/ic200004y. Epub 2011 Jun 28.
In order to find multifunction anticancer complexes, three Mn(II) complexes of N-substituted di(2-pyridylmethyl)amine were characterized and used as agents to interfere with the functions of mitochondria and the metabolite of O(2) in cancer cells. It was found that carboxylate-bridged dimanganese(II) systems are good models of catalase and exhibit good inhibition of the proliferation of U251 and HeLa cells. The inhibiting activity of these manganese(II) complexes on the tumor cells in vitro was related to their disproportionating H(2)O(2) activity. The reaction of carboxylate-bridged dimanganese Mn(II) complex with H(2)O(2) forms a stable Mn(III)-(μ-O)(2)-Mn(IV) complex. Extensive experimental results show that chloride-bridged dimanganese(II) complexes could inhibit the swelling of calcium(II) overloaded mitochondria, and carboxylate-bridged manganese(II) complexes enhance the swelling of calcium(II) overloaded mitochondria. These results indicate that the interactions between Mn(II) complexes of N-substituted di(picolyl)amine and mitochondria are influenced by the structure and conformation of the complexes. Mn(II) complexes of N-substituted di(picolyl)amine could be developed as multifunctional anticancer complexes to interfere with the absorption of calcium(II) in mitochondria and the metabolite of O(2) through the H(2)O(2) or ROS involved signaling induced apoptosis of cancer cells.
为了寻找多功能抗癌配合物，我们对三种 N-取代二（2-吡啶甲基）胺的 Mn(II)配合物进行了表征，并将其用作干扰线粒体功能和癌细胞中 O(2)代谢物的试剂。结果发现，羧酸桥联的双核锰(II)体系是过氧化氢酶的良好模型，对 U251 和 HeLa 细胞的增殖具有良好的抑制作用。这些锰(II)配合物在体外对肿瘤细胞的抑制活性与其歧化 H(2)O(2)的活性有关。羧酸桥联双核 Mn(II)配合物与 H(2)O(2)的反应形成稳定的 Mn(III)-(μ-O)(2)-Mn(IV)配合物。大量实验结果表明，氯化桥联双核锰(II)配合物可以抑制钙(II)超载线粒体的肿胀，而羧酸桥联锰(II)配合物则增强钙(II)超载线粒体的肿胀。这些结果表明，N-取代二吡啶基胺的 Mn(II)配合物与线粒体之间的相互作用受配合物的结构和构象的影响。N-取代二吡啶基胺的 Mn(II)配合物可以通过 H(2)O(2)或 ROS 参与的信号转导诱导细胞凋亡，作为多功能抗癌配合物来干扰线粒体对钙(II)的摄取和 O(2)代谢物。
