Anticancer Activity of Bifunctional Organometallic Ru(II) Arene Complexes Containing a 7-Hydroxycoumarin Group

Abstract

Three organometallic Ru(arene) compounds bearing 7-hydroxycoumarin have been designed and synthesized. Resulting Ru(II) complexes 2–4 showed potent cytotoxicity against the tested cancer cell lines, much higher than either the ligand L1 or unfunctionalized complex 1 alone. Further study indicated complexes 2–4 can activate the expression of Bax, induce cytochrome c release from the mitochondria, and finally activate caspase-3, hinting that these compounds probably induce cell apoptosis by mitochondrial pathway. Additional molecular docking study showed that complexes 2–4 have the potential to bind with the MEK1, and Western blot analysis confirmed that the Ru(II) complexes can prevent the phosphorylation of MEK1 and ERK1 in HCT116 cells, which helps us to further understand the anticancer mechanisms of the newly synthesized complexes. Overall, our research suggested that the ruthenium-coumarin complexes could induce cell apoptosis via inhibition of the mitochondrial and ERK signal pathways.