Stabilization for loop isomers of c-myc G-quadruplex DNA and anticancer activity by ruthenium complexes

In this study, two similar ruthenium(II) complexes 1 and 2 were synthesized to explore their selectivity for binding loop isomers of the c-myc G-quadruplex. The results show that both complexes can efficiently bind the c-myc G-quadruplex DNA, although complex 2 exhibited higher binding affinity. Studies of G-quadruplex loop isomers revealed that the c-myc G-quadruplexes on complexes 1 and 2 may contribute to the selectivity of 1: 2: 1 loop isomers as well as the high affinity of complex 2. This work also found that complex 2 significantly inhibited HeLa cell proliferation and was considerably less toxic to normal cells (Hs-68). Flow cytometric analysis showed that complex 2 induced cell apoptosis by mitochondrial pathways and inhibited the generation of intracellular reactive oxygen species (ROS).