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聚合物-钴(III)配合物:金属螯合物与DNA相互作用的结构分析及细胞毒性活性比较

Polymer-cobalt(III) complexes: structural analysis of metal chelates on DNA interaction and comparative cytotoxic activity.

作者信息

Nehru Selvan, Arunachalam Sankaralingam, Arun Renganathan, Premkumar Kumpati

机构信息

a School of Chemistry, Bharathidasan University , Tiruchirappalli , Tamil Nadu , 620 024 , India .

出版信息

J Biomol Struct Dyn. 2014;32(11):1876-88. doi: 10.1080/07391102.2013.836460. Epub 2013 Sep 20.

Abstract

A new series of pendant-type polymer-cobalt(III) complexes, Co(LL)2(BPEI)Cl, (where BPEI = branched polyethyleneimine, LL = dipyrido3,2-a:2',3'-cphenazine (dpqc), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) and imidazo[4,5-f]1,10-phenanthroline (ip)) each with three different degrees of coordination have been synthesized and characterized. Studies to know the mode and strength of interaction between these polymer-metal complexes and calf thymus DNA have been performed by UV-Visible absorption and emission techniques. Among these series, each polymer metal complex having higher binding strength with DNA has been selected to test against human cancer/normal cell lines. On the basis of these spectral studies, it is proposed that our polymer-metal complexes bind with DNA mainly through intercalation along with some electrostatic binding. The order of binding strength for the complexes with ligand, dpqc > dpq > ip. The analysis of the results suggests that polymer-cobalt(III) complexes with higher degree of coordination effectively binds with DNA due to the presence of large number of positively charged cobalt(III) chelates in the polymer chain which cooperatively act to increase the overall binding strength. These polymer-cobalt(III) complexes with hydrophobic ligands around the cobalt(III) metal centre favour the base stacking interactions via intercalation. All the complexes show very good anticancer activities and increasing of binding strength results in higher inhibition value. The polymer-cobalt(III) complex with dpqc ligand possess two fold increased anticancer activity when compared to complexes with other ligands against MCF-7 cells. Besides, the complexes were insensitive towards the growth of normal cells (HEK-293) at the IC50 concentration.

摘要

合成并表征了一系列新型的 pendant 型聚合物 - 钴(III)配合物,Co(LL)2(BPEI)Cl,(其中 BPEI = 支化聚乙烯亚胺,LL = 二吡啶并[3,2 - a:2',3'- c](6,7,8,9 - 四氢)吩嗪 (dpqc)、二吡啶并[3,2 - d:2',3'- f]喹喔啉 (dpq) 和咪唑并[4,5 - f]1,10 - 菲咯啉 (ip)),它们各自具有三种不同的配位程度。通过紫外 - 可见吸收和发射技术开展了研究,以了解这些聚合物 - 金属配合物与小牛胸腺 DNA 之间相互作用的方式和强度。在这些系列中,已选择每种与 DNA 具有较高结合强度的聚合物金属配合物对人类癌症/正常细胞系进行测试。基于这些光谱研究,提出我们的聚合物 - 金属配合物与 DNA 的结合主要通过插入作用以及一些静电结合。配合物与配体的结合强度顺序为 dpqc>dpq>ip。结果分析表明,具有较高配位程度的聚合物 - 钴(III)配合物由于聚合物链中存在大量带正电荷的钴(III)螯合物,这些螯合物协同作用以增加整体结合强度,从而有效地与 DNA 结合。这些在钴(III)金属中心周围带有疏水配体的聚合物 - 钴(III)配合物有利于通过插入作用进行碱基堆积相互作用。所有配合物均表现出非常好的抗癌活性,结合强度的增加导致更高的抑制值。与其他配体的配合物相比,具有 dpqc 配体的聚合物 - 钴(III)配合物对 MCF - 7 细胞的抗癌活性提高了两倍。此外,在 IC50 浓度下,这些配合物对正常细胞(HEK - 293)的生长不敏感。

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