Synthesis, characterization and biological activity of platinum(II) complexes with a tetrapyrazole ligand

被引：12

作者：

Higuera-Padilla, Angel R. ^{[1
]}

Capote, Jorlis ^{[1
,2
]}

Ortega, Dianela ^{[1
]}

Castro, William ^{[1
]}

Rodriguez-Cordero, Mildred ^{[3
]}

Coll, David ^{[4
]}

Hernandez-Medina, Fernando ^{[5
]}

Fernandez-Mestre, Mercedes ^{[5
]}

Urdanibia, Izaskun ^{[6
]}

Taylor, Peter ^{[6
]}

Rodriguez, Barbara ^{[7
]}

Karam, Arquimedes ^{[8
]}

机构：

[1] IVIC, Lab Quim Bioinorgan, Ctr Quim, Caracas 1020A, Venezuela

[2] Cent Univ Venezuela, Caracas, Venezuela

[3] Univ Simon Bolivar, Lab Quim Bioinorgan, Caracas 1080, Venezuela

[4] IVIC, Lab Quim Computac, Ctr Quim, Caracas 1020A, Venezuela

[5] IVIC, Lab Fisiopatol Secc Inmunogenet, Ctr Med Expt, Caracas 1020A, Venezuela

[6] IVIC, Lab Patol Celular & Mol, Ctr Med Expt, Caracas 1020A, Venezuela

[7] Pontificia Univ Catolica Chile, Dept Quim Inorgan, Fac Quim, Santiago 609441, Chile

[8] IVIC, Lab Polimeros, Ctr Quim, Caracas 1020A, Venezuela

来源：

POLYHEDRON | 2015年 / 102卷

关键词：

Anticancer activity; Platinum complexes; DNA; Thioredoxin reductase; Tetrapyrazole ligand; METAL-BASED CHEMOTHERAPY; DNA-BINDING; KETOCONAZOLE COMPLEXES; THIOREDOXIN REDUCTASE; TROPICAL DISEASES; GOLD COMPOUNDS; CYTOTOXICITY; COPPER(II); AGENTS; CLOTRIMAZOLE;

D O I：

10.1016/j.poly.2015.09.065

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

In the search of an effective chemotherapy for the treatment of cancer, in this work we describe the synthesis, characterization and biological activity of two new platinum complexes. The general formula is [Pt-2(L)(X)(4)], where L was 1,2,4,5-tetrakis((1H-pyrazol-1-yl)methyl)benzene and X were iodine (1) and chlorine (2). The most probable structure was established through a combination of spectroscopic analysis and density functional theory (DFT) calculations. Studies of interaction of complexes with DNA were carried out, and the results by spectroscopic titrations, thermal denaturation and viscosity, showed noncovalent interactions of complexes with DNA. The comet assay showed damage to cellular DNA Inhibition assays of thioredoxin reductase (TrxR) were carried out, and the compounds showed notable inhibitory activity on the enzyme in a concentration dependent manner, with IC50 values of 3.9 and 3.5 nM for 1 and 2 respectively. Complex 2 exhibited greater inhibitory effects than complex 1 against all the tumor cell lines, with growth inhibitory effects superior to cisplatin in some cases. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：321 / 328

页数：8

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