Ruthenium(II) complexes as apoptosis inducers by stabilizing c-myc G-quadruplex DNA

• Two ruthenium(II) complexes have been synthesized by using microwave-assisted technology.
• Both complexes exhibit promising inhibitory activity against MDA-MB-231 cells with low toxicity.
• Both complexes can induce apoptosis of MDA-MB-231 cells by stabilizing the conformation of c-myc G4 DNA.

Two ruthenium(II) complexes, [Ru(L)2(p-tFMPIP)](ClO4)2 (L = bpy, 1; phen, 2; p-tFMPIP = 2-(4-(trifluoromethyphenyl)-1H-imidazo[4,5f][1,10] phenanthroline)), were prepared by microwave-assisted synthesis technology. The inhibitory activity evaluated by MTT assay shown that 2 can inhibit the growth of MDA-MB-231 cells with inhibitory activity (IC50) of 16.3 μM, which was related to the induction of apoptosis. Besides, 2 exhibit low toxicity against normal HAcat cells. The inhibitory growth activity of both complexes related to the induction of apoptosis was also confirmed. Furthermore, the studies on the interaction of both complexes with c-myc G4 DNA shown that 1 and 2 can stabilize the conformation of c-myc G4 DNA in groove binding mode, which has been rational explained by using DFT theoretical calculation methods. In a word, this type of ruthenium(II) complexes can act as potential apoptosis inducers with low toxicity in clinic by stabilizing c-myc G4 DNA.

This type of ruthenium(II) complexes can be used as potential candidate with low toxicity by stabilizing the c-myc G4-DNA, resulting in tumor cells apoptosis (see Figure).Figure optionsDownload as PowerPoint slide