Isoquinoline derivatives Zn(II)/Ni(II) complexes: Crystal structures, cytotoxicity, and their action mechanism

Three transition metal complexes with isoquinoline derivatives: [(MPDQ)(2)Zn(C2H5OH)ClO4]ClO4 (1) (MPDQ = 4,5-methylenedioxy-1-pyridinedihydroisoquinoline), [(PYP)(2)Zn(H2O)](ClO4)(2) (2) (PYP = 5pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline) and [(MPDQ)(2)Ni(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. (C) 2015 Elsevier Masson SAS. All rights reserved.