Copper(II) Nitroaromatic Schiff Base Complexes: Synthesis, Biological Activity and Their Interaction with DNA and Albumins

Darliane A Martins,João Ernesto De Carvalho,Lucius F Bomfim Filho,Ângelo De Fátima,Sonia R W Louro,Maria De Nazaré C Soeiro,Letícia R Teixeira,Denise G J Batista,Cleiton M Da Silva

doi:10.5935/0103-5053.20160150

Darliane A Martins, João Ernesto De Carvalho + Show 7 more

Open Access

https://doi.org/10.5935/0103-5053.20160150

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Abstract

Copper(II) complexes of the Schiff base ligands 2-((5-nitrofuran-2-yl)methyleneamino)phenol (HL1) and 2-(4-nitrobenzylideneamino)phenol (HL2) were prepared and characterized using physicochemical and spectroscopic techniques. In these complexes the Schiff base ligands acted as a bidentate donor bound to Cu2+ through the oxygen and nitrogen atoms in the deprotonated form. The electron paramagnetic resonance spectra, carried out on [CuCl(L1)(phen)].0.5H2O and [CuCl(L2)(phen)].2H2O complexes, showed the presence of only mononuclear forms. The Cu2+ complexes and ligands were evaluated for their in vitro trypanocidal activity. The complex [CuCl(L1)(phen)].0.5H2O was more active than the free Schiff base and also presented a superior effect to benznidazole, the reference drug. The antiproliferative activity of the Schiff bases and Cu2+ complexes were evaluated for their effect on seven tumor cell lines and showed a cytostatic and in some cases a cytotoxic effect. These compounds also presented binding properties to deoxyribonucleic acid (DNA) and moderate ability to quench the intrinsic fluorescence of albumins.

Highlights

The aldimines, known as Schiff bases, are characterized by the presence of a nitrogen which is double bonded to a carbon atom C=N–R (R = H, alkyl or aryl).[1,2] The Schiff bases are widely used as pigments, colorants, catalysts, intermediates in organic synthesis and polymer stabilizers
The Ksv values were calculated by the ratio of the slope to the intercept in a plot of I0/I versus compound concentration and showed that the quenching of CT‐deoxyribonucleic acid (DNA)‐ethidium bromide (EB), by the compounds, was in agreement with the linear Stern-Volmer equation, indicating that EB was replaced in the calf-thymus DNA (CT-DNA)-EB complex by each compound resulting in a decrease in the fluorescence intensity
The results demonstrated that CT-DNA binding affinity was higher for compound 1, followed by 2, HL1 and HL2, which is in agreement with the calculated Kb values

Summary

Introduction

The CT-DNA-EB fluorescence quenching, in the presence of the Schiff bases and their copper(II) complexes, was analyzed according to the Stern-Volmer equation (equation 2): Fo/F = 1 + KSV[Q] The Schiff bases, HL1 and HL2 and [CuCl2(phen)] presented a low to moderated effect on trypomastigotes of T. cruzi, showing EC50 values in the 7-40 μmol L-1 range.

Results

Conclusion