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无机药物化学课题组/药物化学生物学课题组陈金香/陈文华教授以共同通讯作者在Dalton Trans.上发表研究论文

无机药物化学课题组/药物化学生物学课题组陈金香/陈文华教授

以共同通讯作者在Dalton Trans.上发表研究论文

近日,无机药物化学课题组/药物化学生物学课题组陈金香/陈文华教授以共同通讯作者在Dalton Trans.上发表题为“Five water-soluble zwitterionic copper(II)-carboxylate polymers: role of dipyridyl coligands in enhancing the DNA-binding, cleaving and anticancer activities”研究论文。

该研究通过引入稠环辅助配体的方法构建了一系列金属有机骨架材料,并系统研究了此类材料与DNA的结合能力和对DNA的切割活性,并采用MTT法研究了此类化合物对不同肿瘤细胞的抑制活性。研究结果发现,引入辅助配体邻菲罗啉构建的化合物与DNA具有很强的结合活性,同时能有效的对DNA进行切割,对不同肿瘤细胞的抑制活性均比顺铂要强一个数量级,尤其对顺铂耐药的A549细胞株亦表现出了良好的抑制活性,有望作为抗肿瘤药物进行深入研究。

该论文均受到广州市珠江科技新星专项基金、国家自然科学基金的资助,论文第一作者为2014届硕士研究生陈明。Dalton Trans.均为大类化学和小类无机化学与核化学2区杂志,IF=4.197。

Chen, M.; Tang, X. Y.; Yang, S. P.; Li, H. H.; Zhao, H. Q.; Jiang, Z. H.; Chen, J. X*.; Chen, W. H.* Five water-soluble zwitterionic copper(II)-carboxylate polymers: role of dipyridyl coligands in enhancing the DNA-binding, cleaving and anticancer activities, Dalton Trans. 2015, 44, 13369-13369.

Abstract

Five water-soluble zwitterionic copper-carboxylate polymers were prepared from the reaction of N-carboxymethyl-(3,5-dicarboxyl)pyridinium bromide (H3CmdcpBr) with Cu(NO3)2 in the presence of NaOH, by modulating the temperature, solvent and ancillary dipyridyl ligands. These complexes include a 1D ladder-shaped polymer {[Cu3(Cmdcp)2(OH)2(H2O)2]·H2O}n (1) formed in H2O at room temperature, and a 2D network polymer {[Cu(Cmdcp) (H2O)2]·2H2O}n (2) isolated in H2O at 135 °C. At 100 °C in H2O/DMF, the same reaction in the presence of an additional 2,2’-bipyridine (bipy) gave a 2D zwitterionic complex {[Cu(Cmdcp)(bipy)]·3H2O}n (3), together with a 1D double-stranded polymer {[Cu(Cmdcp)(H2O)2]·H2O}n (4) as a minor product. Replacement of bipy with phenanthroline (phen) afforded a 1D zigzag chain polymer {[Cu(Cmdcp)(phen)(H2O)]2·9H2O}5 (5). All these complexes were characterized by IR, elemental analyses and single crystal X-ray crystallography. Agarose gel electrophoresis (GE) and ethidium bromide (EB) displacement experiments indicated that complex 5 exhibited the highest pBR322 DNA cleaving ability with the catalytic efficiency (kmax/KM) of 14.80 h−1·mM−1, and the highest binding affinity toward calf-thymus DNA. MTT assay indicated that complex 5 showed significant inhibitory activity toward the proliferation of several tumor cells. Its IC50 value was at micromolar level and lower than those of cisplatin and complexes 1-4, especially toward resistant lung adenocarcinoma cell A549.