Cinnamaldehyde and cuminaldehyde thiosemicarbazones and their copper(II) and nickel(II) complexes: A study to understand their biological activity

被引:88
作者
Bisceglie, Franco [1 ,2 ]
Pinelli, Silvana [2 ,3 ]
Alinovi, Rossella [2 ,3 ]
Goldoni, Matteo [3 ,4 ]
Mutti, Antonio [3 ]
Camerini, Alessandro [1 ]
Piola, Lorenzo [1 ]
Tarasconi, Pieralberto [1 ,2 ]
Pelosi, Giorgio [1 ,2 ]
机构
[1] Univ Parma, Dept Chem, I-43124 Parma, Italy
[2] CLRCMSB, Parma Local Unit, I-43124 Parma, Italy
[3] Univ Parma, Dept Clin & Expt Med, I-43126 Parma, Italy
[4] Univ Parma, Res Ctr, Workers Compensat Author INAIL, I-43126 Parma, Italy
关键词
Thiosemicarbazone; Nickel; Copper; Caspase; DNA; Topoisomerase IIa; CIRCULAR-DICHROISM; METAL-COMPLEXES; CRYSTAL-STRUCTURE; IN-VITRO; DNA; DERIVATIVES; ALDEHYDES; PYRIDINE;
D O I
10.1016/j.jinorgbio.2014.07.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This paper reports the synthesis and characterization of trans-cinnamaldehyde thiosemicarbazone (Htcin), cuminaldehyde thiosemicarbazone (Htcum) and their copper and nickel complexes. All the compounds, which on healthy cells (human fibroblasts) show a neglectable cytotoxicity, were screened in vitro in cell line 13937 for their antileukemic activity. These compounds, in spite of their molecular similarity, present variegated behaviors. Htcin shows no inhibition activity in 13935 cells, while both its metal complexes inhibit proliferation with IC50 at mu M concentrations. The other ligand, Htcum, and its metal complexes, besides inhibiting proliferation, induce apoptosis. The cell cycle analysis highlights a G(2)/M checkpoint stop suggesting a possible direct action on DNA or on topoisomerase IIa. From CD and UV spectroscopy experiments, the DNA results to be not the main target of all these molecules, while both copper complexes are effective topoisomerase Ha inhibitors. All of these molecules activate caspase-9 and caspase-3, while caspase-8 activity is significantly induced by both cinnamaldehyde metal complexes. Tests on PgP and intracellular metal concentrations (determined by mean of atomic absorption spectrometry) show that the compounds tend to accumulate in the cytoplasm and that the cells do not manage to pump out copper and nickel ions. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:111 / 125
页数:15
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