Isoquinoline derivatives Zn(II)/Ni(II) complexes: Crystal structures, cytotoxicity, and their action mechanism.
Eur J Med Chem
; 100: 68-76, 2015 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-26071859
ABSTRACT
Three transition metal complexes with isoquinoline derivatives [(MPDQ)2Zn(C2H5OH)ClO4]ClO4 (1) (MPDQ = 4,5-methylenedioxy-1-pyridinedihydroisoquinoline), [(PYP)2Zn(H2O)](ClO4)2 (2) (PYP = 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline) and [(MPDQ)2Ni(CH3OH)ClO4]ClO4 (3) were synthesized and fully characterized. All complexes exhibited strong proliferation inhibition activity against various tested cancer cells with high selectivity to tumour and normal cells. BEL-7404 cells were found most sensitive to complex 2 by inducing apoptosis. The process involved the mitochondrial membrane potential depolarization, PARP-proteins cleavage, Bcl-2, p53, p21 expression and caspase family members' activation. Taking these findings into account, it can propose that complex 2 induce cancer cell apoptosis via mitochondrial pathways. The interaction of complex 2 with DNA investigated by fluorescence, CD and viscosity indicated that complex 2 interact with DNA mainly via intercalation.
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Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Zinco
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Isoquinolinas
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Níquel
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Antineoplásicos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article