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含R2edda衍生配体的钯(II)配合物。第二部分。R2eddip酯和钯(II)配合物的合成、表征及体外抗肿瘤研究。

Palladium(II) complexes with R2edda-derived ligands. Part II. Synthesis, characterization and in vitro antitumoral studies of R2eddip esters and palladium(II) complexes.

作者信息

Zmejkovski Bojana B, Kaluderović Goran N, Gómez-Ruiz Santiago, Zizak Zeljko, Steinborn Dirk, Schmidt Harry, Paschke Reinhard, Juranić Zorica D, Sabo Tibor J

机构信息

Department of Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski Trg 12-16, 11000 Belgrade, Serbia.

出版信息

Eur J Med Chem. 2009 Sep;44(9):3452-8. doi: 10.1016/j.ejmech.2009.02.002. Epub 2009 Feb 20.

Abstract

New R(2)eddip-type esters (R = cyclopentyl, L3 x 2 HCl 1.5 H(2)O; cyclohexyl, L4 x 2 HCl x H(2)O) and corresponding palladium(II) complexes, [PdCl(2)L3] (3) and [PdCl(2)L4] x H(2)O (4), as well as [PdCl(2)L2] (2; L2 diisobutyl ester of eddip) were synthesized and characterized by IR, (1)H and (13)C NMR spectroscopies and elemental analysis. The crystal structure of L3 x 2 HCl x 2 CHCl(3) was resolved and is given herein. The NMR spectroscopy confirmed the presence of two isomers (from three possible) for each palladium(II) complex. DFT calculations support the formation of two diastereoisomers. In addition, antitumoral investigations were performed and these investigations also included the diisopropyl ester of eddip (L1) and corresponding palladium(II) complex, [PdCl(2)L1] (1). In vitro antiproliferative activity was determined against several tumor cell lines HeLa, Fem-x, K562 and rested and stimulated normal immunocompetent cells (human peripheral blood mononuclear cells--PBMCs) using MTT test.

摘要

合成了新型R(2)eddip型酯(R = 环戊基,L3·2HCl·1.5H₂O;环己基,L4·2HCl·H₂O)以及相应的钯(II)配合物[PdCl₂L3] (3)和[PdCl₂L4]·H₂O (4),还有[PdCl₂L2] (2;L2为eddip的二异丁酯),并通过红外光谱、¹H和¹³C核磁共振光谱以及元素分析对其进行了表征。解析了L3·2HCl·2CHCl₃的晶体结构并在此给出。核磁共振光谱证实每种钯(II)配合物存在两种异构体(从三种可能的异构体中)。密度泛函理论计算支持两种非对映异构体的形成。此外,还进行了抗肿瘤研究,这些研究还包括eddip的二异丙酯(L1)和相应的钯(II)配合物[PdCl₂L1] (1)。使用MTT试验测定了对几种肿瘤细胞系HeLa、Fem-x、K562以及静止和刺激后的正常免疫活性细胞(人外周血单个核细胞——PBMCs)的体外抗增殖活性。

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