Correlation between DNA interactions and cytotoxic activity of four new ternary compounds of copper(II) with N-donor heterocyclic ligands

被引：67

作者：

Silva, Priscila P. ^{[1
]}

Guerra, Wendell ^{[1
]}

dos Santos, Geandson Coelho ^{[1
]}

Fernandes, Nelson G. ^{[1
]}

Silveira, Josiane N. ^{[2
]}

da Costa Ferreira, Ana M. ^{[3
]}

Bortolotto, Tiago ^{[4
]}

Terenzi, Hernan ^{[4
]}

Bortoluzzi, Adailton Joao ^{[5
]}

Neves, Ademir ^{[5
]}

Pereira-Maia, Elene C. ^{[1
]}

机构：

[1] Univ Fed Minas Gerais, Dept Quim, BR-31270901 Belo Horizonte, MG, Brazil

[2] Univ Fed Minas Gerais, Dept Anal Clin & Toxicol, BR-31270901 Belo Horizonte, MG, Brazil

[3] Univ Sao Paulo, Inst Quim, BR-05508000 Sao Paulo, Brazil

[4] Univ Fed Santa Catarina, Dept Bioquim, Ctr Biol Mol Estrutural, BR-88040970 Florianopolis, SC, Brazil

[5] Univ Fed Santa Catarina, Dept Quim, BR-88040970 Florianopolis, SC, Brazil

来源：

JOURNAL OF INORGANIC BIOCHEMISTRY | 2014年 / 132卷

关键词：

Ternary copper compounds; Cytotoxicity; DNA binding; DNA cleavage; Cellular concentration; DOUBLE-STRAND CLEAVAGE; IN-VITRO CYTOTOXICITY; NUCLEASE ACTIVITY; MIXED CHELATE; COMPLEXES; 1,10-PHENANTHROLINE; MECHANISM; BINDING; DAMAGE; COORDINATION;

D O I：

10.1016/j.jinorgbio.2013.09.014

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：

Four new ternary complexes of copper(II) were synthesized and characterized: [Cu(hyd)(bpy)(acn)(ClO4)](ClO4)] (1), [Cu(hyd)(phen)(acn)(ClO4)](ClO4)] (2), [Cu(Shyd)(bpy)(acn)(ClO4)](ClO4)1 (3) and [Cu(Shyd)(phen)(acn) (ClO4)](ClO4)] (4), in which acn = acetonitrile; hyd = 2-furoic acid hydrazide, bpy = 2,2-bipyridine; phen = 1,10-phenanthroline and Shyd = 2-thiophenecarboxylic acid hydrazide. The cytotoxic activity of the complexes in a chronic myelogenous leukemia cell line was investigated. All complexes are able to enter cells and inhibit cellular growth in a concentration-dependent manner, with an activity higher than that of the corresponding free ligands. The substitution of Shyd for hyd increases the activity, while the substitution of bpy for phen renders the complex less active. Therefore, the most potent complex is 4 with an IC50 value of 1.5 +/- 02 mu M. The intracellular copper concentration needed to inhibit 50% of cell growth is approximately 7 x 10(-15) mol/cell. It is worth notifying that a correlation between cytotoxic activity, DNA binding affinity and DNA cleavage was found: 1 < 3 < 2 < 4. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：67 / 76

页数：10

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