Synthesis, hydrolytic DNA-cleaving activities and cytotoxicities of EDTA analogue-tethered pyrrole-polyamide dimer-based Ce(IV) complexes
Synthesis, hydrolytic DNA-cleaving activities and cytotoxicities of EDTA analogue-tethered pyrrole-polyamide dimer-based Ce(IV) complexes
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EDTA 类似物系链吡咯-聚酰胺二聚体 Ce(IV) 复合物的合成、水解 DNA 切割活性和细胞毒性
DOI：
10.1016/j.ejmech.2014.09.057
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发表时间：
2014
影响因子：
6.7
通讯作者：
Chen Wen-Hua
中科院分区：
文献类型：
--
作者：
Yang Jian-Wei;Lin Yan-Ling;Dong Cheng;Zhou Chun-Qiong;Chen Jin-Xiang;Wang Bo;Zhou Zhong-Zhen;Sun Bin;Chen Wen-Hua
合成并表征了两种EDTA类似物-栓系的C2-对称二聚吡咯-聚酰胺5和二吡咯-聚酰胺6及其相应的Ce（IV）配合物Ce-5和Ce-6。琼脂糖凝胶电泳研究表明，配合物Ce-5和Ce-6在生理条件下具有较强的DNA切割活性。最大一级反应速率常数（kmax）分别为（0.42 ± 0.02）h− 1（Ce-5）和（0.52 ± 0.02）h− 1（Ce-6），表明这两种配合物对超螺旋DNA的催化裂解高达约108倍。配合物Ce-6的总催化活性（kmax/KM）比Ce-5高约10倍，这可能是由于其较高的DNA结合亲和力。抑制实验和模型研究表明，配合物Ce-5和Ce-6具有水解DNA的切割作用。此外，这两种配合物被发现对A549和HepG-2细胞显示中等抑制活性。
Two EDTA analogue-tetheredC2-symmetrical dimeric monopyrrole-polyamide5and dipyrrole-polyamide6, and their corresponding Ce(IV) complexes Ce-5and Ce-6were synthesized and fully characterized. Agarose gel electrophoresis studies on pBR322 DNA cleavage indicate that complexes Ce-5and Ce-6exhibited potent DNA-cleaving activities under physiological conditions. The maximal first-order rate constants (kmax's) were (0.42 ± 0.02) h−1for Ce-5and (0.52 ± 0.02) h−1for Ce-6, respectively, suggesting that both complexes catalyzed the cleavage of supercoiled DNA by up to approximately 108-fold. Complex Ce-6exhibitedca10-fold higher overall catalytic activity (kmax/KM) than Ce-5, which may be ascribed to its higher DNA-binding affinity. Inhibition experiments and a model study convincingly suggest that both complexes Ce-5and Ce-6functioned as hydrolytic DNA-cleavers. In addition, both complexes were found to display moderate inhibitory activity toward A549 and HepG-2 cells.