Search

Three transition metal complexes with isoquinoline derivatives: [(MPDQ) 2 Zn(C 2 H 5 OH)ClO 4 ]ClO 4 ( 1 ) (MPDQ = 4,5-methylenedioxy-1-pyridinedihydroisoquinoline), [(PYP) 2 Zn(H 2 O)](ClO 4 ) 2 ( 2 ) (PYP = 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline) and [(MPDQ) 2 Ni(CH 3 OH)ClO 4 ]ClO 4 ( 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. [ABSTRACT FROM AUTHOR]

[Pt(Q) 2 ] ( 1 ) and [Pt(MQ) 2 ] ( 2 ) exhibited enhanced cytotoxicity against BEL-7404, Hep-G2, NCI–H460, T-24, A549 tumor cells but low cytotoxicity on normal HL-7702 cells. 1 and 2 could cause the cell cycle arrest in G2 and S phase, respectively. While pifithrin-α, a specific p53 inhibitor, induced cell cycle arrest in G1 phase. Although 1 , 2 and pifithrin-α caused serious inhibition on p53, 1 and 2 significantly cause the loss of mitochondrial membrane potential and increase of the reactive oxygen species level, cytochrome c , apaf-1 and caspase-3/9 ratio in BEL-7404 cells. 1 and 2 may trigger the cell apoptosis through a mitochondrial dysfunction pathway whereas pifithrin-α does not. The interactions of 1 and 2 with DNA are most probably via an intercalation. [ABSTRACT FROM AUTHOR]