C-MYC G-QUADRUPLEX STABILIZATION AND CYTOTOXICITY OF AN OXADIAZOLE-BEARING RUTHENNIUM(II) COMPLEX

G-quadruplex DNA, especially the cellular-myelocytomatosis viral oncogene (c-myc) is closely related to the proliferation of tumour cells. In this report, the interaction between the c-myc Pu27/Pu22 DNA and an oxadiazole moiety-containing ruthenium(II) complex, and the further antitumor effect of the complex have been investigated. Results of polymerase chain reaction (PCR)-stop assay and color reaction studies proved that the complex can induce the formation of c-myc G-quadruplex DNA from Pu27 and Pu22 oligonucleotides. As verified by fluorescence resonance energy transfer (FRET) assay and luminescence titrations, the complex can selectively bind to and stabilize c-myc G-quadruplex DNA in high binding affinity with the binding constants and Delta Tm values of 6.60 x 105 M-1 and 9.5 degrees C for Pu27, and 1.75 x 106 M-1 and 7.0 degrees C for Pu22, respectively. The complex interacted with c-myc G-quadruplex DNA with 1:1 (Pu27) and 2:1 (Pu22) [complex]/ [quadruplex] binding stoichiometry as determined by continuous variation analysis. The experiments on cytotoxicity of the complex revealed that it moderately inhibits the proliferation of MCF-7 and HepG-2 cancer cells through apoptosis pathway and exhibits selectivity between tumor cells and normal cells.