Tetramethyl-phenanthroline copper complexes in the development of drugs to treat cancer: synthesis, characterization and cytotoxicity studies of a series of copper(II)-L-dipeptide-3,4,7,8-tetramethyl-phenanthroline complexes

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Tetramethyl-phenanthroline copper complexes in the development of drugs to treat cancer: synthesis, characterization and cytotoxicity studies of a series of copper(II)-L-dipeptide-3,4,7,8-tetramethyl-phenanthroline complexes

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ACTIVIDAD CITOTOXICA

Abstract

New compounds to fght cancer are needed due to cancer high incidence and lack of curative treatments for several classes of this disease. Metal-based coordination compounds ofer a variety of molecules that can turn into drugs. Among them, coordi nation copper complexes are emerging as an attractive class of compounds for cancer treatment. A series of [Cu(l-dipeptide) (tmp)] (tmp=3,4,7,8-tetramethyl-1,10-phenanthroline) complexes were synthesized and characterized in the solid state, including the determination of the crystalline structure of [Cu(Gly-Gly)(tmp)]·3.5 H2O and [Cu2Cl4(tmp)2]. The complexes were studied in solution, where the major species are also ternary ones. The lipophilicity of the complexes was determined and the binding to the DNA was evaluated, suggesting that it occurs in the DNA’s major groove. The cytotoxicity of the com plexes was evaluated on diferent cancer cell lines: human metastatic breast adenocarcinoma MDA-MB-231 (triple negative, ATCC: HTB-26), MCF-7 (ATCC: HTB-22), SK-BR-3 (ATCC: HTB-30), human lung epithelial carcinoma A549 (ATCC: CCL-185), cisplatin resistant-human ovarian carcinoma A2780cis (SIGMA) and nontumoral cell lines: MRC-5 (lung; ATCC: CCL-171) and MCF-10A (breast, ATCC: CRL-10317). [Cu(l-dipeptide)(tmp)] complexes are highly cytotoxic as compared to [Cu(l-dipeptide)(phenanthroline)] and cisplatin. Therefore, [Cu(l-dipeptide)(tmp)] complexes are promising candidates to have their in vivo activity further studied toward new treatments for triple negative breast cancer and other aggressive tumors for which there is no curative pharmacological treatment to the date.

Autor

Leite, Celisnolia M. 
Napoleone, Adriana 
Mendes, Luis F. S. 
Ribeiro, Ronny R.
Ellena, Javier 
Batista, Alzir A.
Costa Filho, Antonio J. 

Fuente

Journal of Biological Inorganic Chemistry, 2022

Editor

Springer

Fecha

2022

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PDF

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Tipo

Artículo

Identificador

10.1007/s00775-022-01938-3

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PDF
Fecha de agregación
June 10, 2022
Colección
Bibliografía Nacional Química
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Document
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Citación
Alvarez, Natalia, “Tetramethyl-phenanthroline copper complexes in the development of drugs to treat cancer: synthesis, characterization and cytotoxicity studies of a series of copper(II)-L-dipeptide-3,4,7,8-tetramethyl-phenanthroline complexes,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed December 8, 2022, http://riquim.fq.edu.uy/items/show/6533.
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