A ruthenium(II) complex capable of inducing and stabilizing bcl-2 G-quadruplex formation as a potential cancer inhibitor

• [Ru(ip)3](ClO4)2·2H2O is capable of selectively binding to bcl-2 G-quadruplexes.
• [Ru(ip)3](ClO4)2·2H2O can well induce the formations of antiparallel G-quadruplex.
• Overlarge ligands of Ru-complexes reduce the induction of bcl-2 G-quadruplexes.
• [Ru(ip)3](ClO4)2·2H2O can enter the nuclei of HeLa cells and induce cell apoptosis.

Two ruthenium(II) complexes (Ru-complexes) were synthesized and characterized in this study. The selectivity and ability of the complexes to interact with bcl-2 DNA were investigated here. It turned out that [Ru(ip)3](ClO4)2·2H2O (complex 1, ip = 1H-iminazole [4,5-f][1,10] phenanthroline) could induce and stabilize the formations of G-quadruplexes more effectively than [Ru(pip)3](ClO4)2·2H2O (complex 2, pip = 2-phenylimidazo-[4,5-f][1,10]phenanthroline) did. Considering the important role of the Ru-complex ligand in inducing and stabilizing the formations of G-quadruplex in our previous studies, we speculate that the overlarge ligand of complex 2 may block its binding affinity for G-quadruplexes. Complex 1 also induced cell apoptosis in in vitro assays. In general, this study provided potentially important information for further development of the Ru-complexes as good inducers and stabilizers of bcl-2 G-quadruplex DNA for cancer treatment.

[Ru(ip)3](ClO4)2·2H2O (complex 1) stabilizes the combination of bcl-2 G-quadruplex to form the antiparallel conformation and causes cell apoptosis mediated by caspase activationFigure optionsDownload as PowerPoint slide