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

Abstract

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) 2 Bipy 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) 2 Phen, Cu(Valp) 2 Bipy and Cu 2 (Valp) 4 , respectively. Cytotoxicity assays demonstrated that V79 cells were more sensitive to Cu II 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) 2 Phen higher than Cu(Valp) 2 Bipy, higher than Cu 2 (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.

Selenylated-oxadiazoles as promising DNA intercalators: Synthesis, electronic structure, DNA interaction and cleavage

“…The solutions were mixed and the absorption spectra were recorded immediately. The experiments were repeated three times and the results obtained were plotted in tables and can be seen on graphics [54].…”

“…Plasmid DNA pBSK II (Stratagene) was obtained and purified according to standard techniques [54]. The DNA cleavage ability of the compounds diluted in acetonitrile was examined to establish their ability to cleavage pBSK II supercoiled DNA (FI) to the open circular (F II) and, linear DNA (F III) through single and double-strand breaks respectively [54].…”

“…Statistical analysis of plasmid experiments was conducted by ANOVA followed by Dunnett's multiple comparison test. The GraphPad Prism 6.0 software was employed and a p-value under 0.05 was considered significant [54].…”

“…Compounds 3a, 3b, 3c are the ones that presented the weakest UV-Vis DNA interaction characteristics and no plasmid DNA cleavage activity, those are the more suitable for developing drugs [55]. Compound 3f showed strong DNA interaction and its ability to cleave may be used for developing DNA markers or anti-cancer drugs [54,65].…”

Nuclease-like metalloscissors: Biomimetic candidates for cancer and bacterial and viral infections therapy

“… [212] 46-Cu pBSK II / oligonucleotide , AGE, d PAGE PC *Cytotoxicity activity: MTT assay *Clonogenic assay. [213] 47-Ru pBR322, AGE, PC *Antibacterial activity. [214] 48-Cu AGE,pET-28b, e OxC * Cytotoxicity activity.…”