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Mixed Ternary Mononuclear Copper(II) Complexes Based on Valproic Acid with 1,10-Phenanthroline and 2,2’-Bipyridine Ligands: DNA Interaction and Cytotoxicity in V79 Cells

This paper reports the DNA interaction and cytotoxicity of binary and ternary copper(II) complexes of valproic acid with phenanthroline or bipyridine and the complementary characterization of Cu(Valp)2Bipy by crystallography. Circular dichroism, plasmid and oligonucleotide assays have shown that the...

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Published in:Journal of the Brazilian Chemical Society 2019-03, Vol.30 (3), p.597-613
Main Authors: Pich, Claus, dos Santos, Paulo, Fortunato, Tatiana, Chiarello, Marilda, de Oliveira, Iuri, Soares, Bárbara, Ghermani, Nour, Machado, Miriana, Roesch-Ely, Mariana, Dumas, Françoise, Terenzi, Hernan, Henriques, João, Moura, Sidnei
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container_issue 3
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container_title Journal of the Brazilian Chemical Society
container_volume 30
creator Pich, Claus
dos Santos, Paulo
Fortunato, Tatiana
Chiarello, Marilda
de Oliveira, Iuri
Soares, Bárbara
Ghermani, Nour
Machado, Miriana
Roesch-Ely, Mariana
Dumas, Françoise
Terenzi, Hernan
Henriques, João
Moura, Sidnei
description This paper reports the DNA interaction and cytotoxicity of binary and ternary copper(II) complexes of valproic acid with phenanthroline or bipyridine and the complementary characterization of Cu(Valp)2Bipy by crystallography. Circular dichroism, plasmid and oligonucleotide assays have shown that the complexes interact with DNA in different manners and are able to cleave plasmid DNA and oligonucleotides at concentrations from 10 to 1000 mol L-1. The plasmid DNA cleavage is enhanced 650, 375 and 285 times by photo activation with UVB light for the complexes Cu(Valp)2Phen, Cu(Valp)2Bipy and Cu2(Valp)4, respectively. Cytotoxicity assays demonstrated that V79 cells were more sensitive to CuII derivatives than sodium valproate as evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) and clonogenic assays, where the cytotoxic profile of the compounds was: Cu(Valp)2Phen higher than Cu(Valp)2Bipy, higher than Cu2(Valp)4. Therefore, we report two copper complexes, which interact with DNA and promote its cleavage, leading to an enhanced cytotoxicity when compared to valproic acid.
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title Mixed Ternary Mononuclear Copper(II) Complexes Based on Valproic Acid with 1,10-Phenanthroline and 2,2’-Bipyridine Ligands: DNA Interaction and Cytotoxicity in V79 Cells
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