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J Inorg Biochem ; 220: 111453, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33895694

RESUMO

The cobalt(II), copper(II) and zinc(II) complexes of 1,10-phenanthroline (phen) and maltol (mal) (complexes 1, 2, 3 respectively) were prepared from their respective metal(II) chlorides and were characterized by FT-IR, elemental analysis, UV spectroscopy, molar conductivity, p-nitrosodimethylaniline assay and mass spectrometry. The X-ray structure of a single crystal of the zinc(II) analogue reveals a square pyramidal structure with distinctly shorter apical chloride bond. All complexes were evaluated for their anticancer property on breast cancer cell lines MCF-7 and MDA-MB-231, and normal cell line MCF-10A, using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and morphological studies. Complex 2 was most potent for 24, 48 and 72 h treatment of cancer cells but it was not selective towards cancer over normal cells. The mechanistic studies of the cobalt(II) complex 1 involved apoptosis assay, cell cycle analysis, dichloro-dihydro-fluorescein diacetate assay, intracellular reactive oxygen species assay and proteasome inhibition assay. Complex 1 induced low apoptosis, generated low level of ROS and did not inhibit proteasome in normal cells. The study of the DNA binding and nucleolytic properties of complexes 1-3 in the absence or presence of H2O2 or sodium ascorbate revealed that only complex 1 was not nucleolytic.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Fenantrolinas/farmacologia , Pironas/farmacologia , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cobalto/química , Complexos de Coordenação/síntese química , Cobre/química , DNA/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Fenantrolinas/síntese química , Inibidores de Proteassoma/síntese química , Inibidores de Proteassoma/farmacologia , Pironas/síntese química , Espécies Reativas de Oxigênio/metabolismo , Zinco/química
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