Dinuclear Copper(I) Complexes Containing Cyclodiphosphazane Derivatives and Pyridyl Ligands: Synthesis, Structural Studies, and Antiproliferative Activity toward Human Cervical and Breast Cancer Cells
Dinuclear Copper(I) Complexes Containing Cyclodiphosphazane Derivatives and Pyridyl Ligands: Synthesis, Structural Studies, and Antiproliferative Activity toward Human Cervical and Breast Cancer Cells
复制标题
DOI：
10.1021/ic100944d
复制
发表时间：
2010-10-04
影响因子：
4.6
通讯作者：
Panda, Dulal
中科院分区：
文献类型：
--
作者：
Balakrishna, Maravanji S.;Suresh, D.;Panda, Dulal
通过八核铜（I）配合物[Cu-8（mu（2）-1）（8）{[（BuNP）-Bu-t（NC_4 H_8X）]（2）}（4）]（3，X = O; 4，X = NMe）与不同的吡啶配体反应，合成了几种混合配体的环二磷腈铜（I）配合物[（BuNP）-Bu-t（NC_4 H_8X）]（2）（1，X = O; 2，X = NMe）.金属大环配合物3或4与吡啶、2，2 ′-联吡啶和1，10-邻菲咯啉相互作用得到中性双核配合物[（C_5H_5N）（4）Cu（2）l（2）{[（BuNP）-Bu-t（NC_4 H_8X）]（2）}]（5，X = O; 6，X = NMe），[（2，2'-bpy）2Cu（2）I（2）{[（BuNP）-Bu-t（NC4H8X）]（2）}]（7，X = O; 8，X = NMe）和[（1，10-phen）（2）Cu（2）I（2）{[（BuNP）-Bu-t-（NC_4H_8X）]（2）}]（9，X = O; 10，X = NMe）的反应。新的双核配合物3、5和7-9被测试了它们对人宫颈癌（HeLa）细胞的细胞毒性倾向。结果表明，所有铜配合物的体外抗肿瘤活性与广泛使用的抗癌药物顺铂相似或更好。在所测试的化合物中，配合物9在HeLa细胞中显示出最有效的抑制活性。此外，发现复合物9有效地抑制人乳腺癌细胞（MCF-7）、高转移性乳腺癌细胞（MDA-MB 231）和未转化的中国仓鼠卵巢（CHO）细胞的增殖。复合物9比顺铂更有效地抑制培养中这些细胞的增殖;例如，发现复合物9比顺铂更有效地抑制HeLa和MCF-7细胞的增殖3倍和5倍。复合物9处理损伤DNA完整性，将细胞阻滞在细胞周期的G1期，并通过p53依赖性途径诱导细胞凋亡。配合物9和10的分子结构通过单晶X-射线衍射研究证实。
Several mixed-ligand copper(I) complexes of cyclodiphosphazanes, [(BuNP)-Bu-t(NC4H8X)](2) (1, X = O; 2, X = NMe), were synthesized by reacting the octanuclear copper(I) complexes [Cu-8(mu(2)-l)(8){[(BuNP)-Bu-t(NC4H8X)](2)}(4)] (3, X = O; 4, X = NMe) with various pyridyl ligands. Interaction of the metallomacrocyclic complex 3 or 4 with pyridine, 2,2'-bipyridine, and 1,10-phenanthroline afforded the neutral dinuclear complexes [(C5H5N)(4)Cu(2)l(2){[(BuNP)-Bu-t(NC4H8X)](2)}] (5, X = O; 6, X = NMe), [(2,2'-bpy)2Cu(2)l(2){[(BuNP)-Bu-t(NC4H8X)](2)}] (7, X = O; 8, X = NMe), and [(1,10-phen)(2)Cu(2)l(2){[(BuNP)-Bu-t-(NC4H8X)](2)}] (9, X =0; 10, X = NMe), respectively, in good yield. The new dinuclear complexes 3, 5, and 7-9 were tested for their cytotoxic propenies against human cervical cancer (HeLa) cells. The results indicated that all of the copper complexes have in vitro antitumor activity either similar to or better than that of cisplatin, a widely used anticancer drug. Among the compounds tested, complex 9 showed the most potent inhibitory activity in HeLa cells. In addition, complex 9 was found to potently inhibit proliferation of human breast cancer cells (MCF-7), highly metastatic breast cancer cells (MDA-MB 231), and nontransformed Chinese hamster ovary (CHO) cells. Complex 9 inhibited proliferation of these cells in culture more potently than cisplatin; for example, complex 9 was found to inhibit proliferation of HeLa and MCF-7 cells 3 and 5 times more efficiently than cisplatin. Complex 9 treatment damaged the DNA integrity, blocked the cells in the G1 phase of the cell cycle, and induced apoptosis via a p53-dependent pathway. The molecular structures of conplexes 9 and 10 were confirmed by single-crystal X-ray diffraction studies.