Binding mode transformation and biological activity on the Ru(II)-DMSO complexes bearing heterocyclic pyrazolyl ligands

Three Ru(II)-DMSO complexes (1-3) containing 2-(3-pyrazolyl)pyridine (PzPy), 2-pyrazol-3-ylfuran (PzO), or 2-pyrazol-3-ylthiophene (PzS) ligand, were synthesized and characterized. The monodentate coordination of the heterocyclic pyrazolyl ligand (Pz(Py)) with Ru(II) ion via N atom was confirmed by single crystal X-ray diffraction. Complex 1 could be converted to the known eta(2)-bidentate Pz(Py) complex cis(Cl), cis(S)4RuCl(2)(Pz(Py))(DMSO)(2)] (4) under reflux conditions. The mechanism underlying binding mode transformation was studied by H-1 NMR spectroscopy and density functional theory (DFT) calculations. The binding abilities of the complexes (1-4) with calf-thymus (CT) DNA and bovine serum albumin (BSA) were investigated using spectroscopic and molecular docking techniques. Among the four Ru(II) complexes, complexes 1 and 3 inhibited the long-term proliferation of human breast cancer cells, whereas complexes 2 and 4 did not inhibit their proliferation to a considerable extent. Interestingly, complexes 1 and 3 did not induce significant cell death but rather attenuated the clonogenicity of breast cancer cells by upregulating reactive oxygen species (ROS), endoplasmic reticulum (ER) and autophagic stress.

Automated summary

Three Ru(II)-DMSO complexes with different ligands were synthesized and characterized. Among them, complexes 1 and 3 showed significant inhibition on the proliferation of human breast cancer cells by upregulating ROS, ER, and autophagic stress without inducing cell death.