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Copper(II) complexes with pyridoxal dithiocarbazate and thiosemicarbazone ligands: crystal structure, spectroscopic analysis and cytotoxic activity

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Abstract

The present study reports the synthesis and crystal structures of Cu(II) complexes with pyridoxal S-allyldithiocarbazate (H2L1) and pyridoxal thiosemicarbazones (H2L2 = pyridoxal-N4-phenyl-3-thiosemicarbazone and H2L3 = pyridoxal-N4-semicarbazone). The single-crystal X-ray study reveals that in all cases, the Schiff base coordinated tridentately through the ONS-donor atoms, resulting in distorted square planar coordination geometries with the copper atoms. The Cu(II) complexes with pyridoxal dithiocarbazate, [Cu(HL1)Cl]·H2O and [Cu(HL1)Br]·H2O, as well as three complexes with pyridoxal thiosemicarbazone, [Cu(HL2)Cl]·dmf, [Cu(HL2)Br]·H2O·dmf and [Cu(H2L3)Br]Br·H2O, were also characterized by spectroscopic and physical–chemical analyses. The cytotoxicity of the complexes toward two kinds of cancerous cells (Ehrlich and S-180 cells) was evaluated by an MTT assay. The complex [Cu(H2L3)Br]Br·H2O was selected to study both the cellular and molecular mechanisms underlying its promising cytotoxicity. The Hoechst 33342/PI dual-staining assay showed the typical apoptotic morphology of cancer cells, and the RT-qPCR analysis revealed that the expressions of Bax, Casp3, Casp8, Casp9 and TP53 were markedly increased in both the Ehrlich and S-180 cells exposed to 10 μM for 3 h. According to our results, this complex induces cell death through apoptosis, showing potential as a future drug against cancer.

Graphical abstract

Five stable copper(II) complexes with pyridoxal have been synthesized and their crystal structure has been studied. Spectroscopy experiments and cytotoxic assays against S-180 and Ehrlich cancer cell lines were performed and showed promising results as novel antitumor drugs.

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Acknowledgements

We gratefully acknowledge the financial support of FAPDF, CAPES, CNPq and FINEP/CTINFRA.

Funding

Funding was provided by Fundação de Apoio à Pesquisa do Distrito Federal Funda de Apoio? Pesquisa do Distrito Federal (Grant No. 0193.001545/2017).

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Authors and Affiliations

  1. Laboratory of Inorganic Synthesis and Crystallography, University of Brasilia (IQ-UnB), Campus Universitário Darcy Ribeiro, Brasília, DF, CEP 70904-970, Brazil

    Claudia C. Gatto, Marcio A. S. Chagas & Iariane J. Lima

  2. Laboratory of Molecular Genetics and Cytogenetics, Federal University of Goiás, Campus Samambaia (Campus II), Goiânia, GO, CEP 74690-900, Brazil

    Francyelli Mello Andrade, Hugo D. Silva, Gabrielly R. Abrantes & Elisângela P. S. Lacerda

  3. University Centre of Goiás (Centro Universitário de Goiás - Uni- ANHANGÜERA), Polo Sede, Goiânia, GO, CEP 74423-115, Brazil

    Hugo D. Silva

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  1. Claudia C. Gatto
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Correspondence to Claudia C. Gatto.

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Gatto, C.C., Chagas, M.A.S., Lima, I.J. et al. Copper(II) complexes with pyridoxal dithiocarbazate and thiosemicarbazone ligands: crystal structure, spectroscopic analysis and cytotoxic activity. Transit Met Chem 44, 329–340 (2019). https://doi.org/10.1007/s11243-018-00299-8

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