New manganese(II), iron(II), cobalt(II), nickel(II) and copper(II) saccharinate complexes of 2,6-bis(2-benzimidazolyl)pyridine as potential anticancer agents.
Eur J Med Chem
; 202: 112535, 2020 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-32653697
ABSTRACT
New mononuclear complexes [Mn(NO3)(sac)(H2O)(bzimpy)]·2DMF (Mn), [Fe(sac)2(H2O)(bzimpy)]·2H2O (Fe), [Co(bzimpy)2](sac)2·2H2O (Co), [Ni(bzimpy)2](sac)2·H2O·i-PrOH (Ni) and [Cu(sac)2(bzimpy)]·3DMF (Cu) (sac = saccharinate and bzimpy = 2,6-bis(2-benzimidazolyl)pyridine) were synthesized and structurally characterized by elemental analysis, UV-Vis, IR, ESI-MS and X-ray diffraction. The anticancer activity of the metal complexes against A549 (lung), MCF-7 (breast), HT29 (colon) cancer cells and MCF10A (normal human breast epithelial) cells was tested and compared with those of cisplatin and bzimpy. The complexes displayed potent cytotoxic activity especially in MCF-7 and A549 cell lines, but they were practically inactive against the normal cells. Mechanistic studies with Mn and Cu complexes on A549 cells indicated that the complexes induced G0/G1 arrest. Both complexes increased intracellular ROS (reactive oxygen species) levels and successfully caused both mitochondrial dysfunction and double-strand DNA breaks. The up-regulated Bax and down-regulated Bcl-2 expression levels, caspase-3/7 activation and reduced Fas expression indicated that Mn and Cu induced ROS-dependent mitochondria-mediated intrinsic apoptosis in A549 cells.
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Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Sacarina
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Benzimidazóis
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Metais Pesados
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Complexos de Coordenação
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Antineoplásicos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article