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立体选择性配体及其配合物。第七部分。(S,S)-乙二胺-N,N′-二(2-(4-甲基)戊酸)O,O′-二烷基酯的铂(II)配合物的合成、表征和体外抗肿瘤活性。

Stereospecific ligands and their complexes. Part VII. Synthesis, characterization and in vitro antitumoral activity of platinum(II) complexes with O,O'-dialkyl esters of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoic acid.

机构信息

Department of Chemistry, Faculty of Science, University of Kragujevac, R Domanovića 12, 34000 Kragujevac, Serbia.

出版信息

Eur J Med Chem. 2011 Sep;46(9):4559-65. doi: 10.1016/j.ejmech.2011.07.034. Epub 2011 Jul 27.

Abstract

Platinum(II) complexes (1-4) with bidentate N,N'-ligands, O,O'-dialkyl esters (alkyl = ethyl, n-propyl, n-butyl and n-pentyl), of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoic acid were synthesized and characterized by IR, (1)H NMR and (13)C NMR spectroscopy and elemental analysis. DFT calculations were performed for the complexes and it was found that only one diastereoisomer could be formed. Cytotoxic activity of complexes 1-4 was determined against chronic lymphocytic leukemia cells (CLL) and compared to the activity of ligand precursors L1 · 2HCl-L4·2HCl and corresponding palladium(II) complexes, [PdCl(2)L] (L = L1-L4). The complexes were found to exhibit significantly higher antitumor activities than cisplatin on CLL cells. Cytotoxic effect of platinum(II) complexes on CLL cells was higher compared to corresponding palladium(II) complexes. In addition the mode of cell death induced by platinum(II) complexes was determined.

摘要

合成了具有双齿 N,N'-配体、O,O'-二烷基酯(烷基=乙基、正丙基、正丁基和正戊基)的(S,S)-乙二胺-N,N'-二-2-(4-甲基)戊酸的铂(II)配合物(1-4),并通过红外光谱、(1)H NMR 和(13)C NMR 光谱及元素分析进行了表征。对配合物进行了密度泛函理论(DFT)计算,发现只能形成一种非对映异构体。测定了配合物 1-4 对慢性淋巴细胞白血病细胞(CLL)的细胞毒性,并与配体前体 L1·2HCl-L4·2HCl 和相应的钯(II)配合物[PdCl2L](L=L1-L4)的活性进行了比较。结果表明,与顺铂相比,这些配合物对 CLL 细胞具有显著更高的抗肿瘤活性。与相应的钯(II)配合物相比,铂(II)配合物对 CLL 细胞的细胞毒性作用更高。此外,还确定了铂(II)配合物诱导 CLL 细胞死亡的模式。

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