Synthesis and antiproliferative activity of benzimidazole-based, trinuclear neutral cyclometallated and cationic, N^N-chelated ruthenium(ii) complexes

Abstract

A series of 2-phenyl and 2-pyridyl tris-benzimidazole ligands was reacted with the [Ru(p-cymene)Cl₂]₂ dimer to yield the corresponding neutral cyclometallated and cationic organoruthenium(II) complexes. All of the synthesized compounds were characterized using an array of spectroscopic and analytical techniques, including ¹H, ¹³C nuclear magnetic resonance (NMR), infrared spectroscopy and mass spectrometry. The trinuclear compounds were screened for their cytotoxicy against the MCF-7 breast cancer cell line and the triple negative MDA-MB-231 breast cancer cell line at concentrations of 10 and 20 μM. Overall, the 2-pyridyl ligands 10 and 11, and their corresponding trinuclear complexes [16][PF₆]₃ and [17][PF₆]₃, show the most promising activity as these compounds significantly reduce the percentage cell survival of MCF-7 and MDA-MB-231 breast cancer cell lines at the aforementioned fixed concentrations. It was observed that 10 and [16][PF₆]₃ show potency greater than that of cisplatin against the MCF-7 breast cancer cell line, and [17][PF₆]₃ shows potency comparable to that of cisplatin against the MCF-7 cell line. Additionally, the synthesized compounds were observed to have relatively low cytotoxicty towards MCF-12A breast epithelial cells and relatively higher selectivity towards MCF-7 breast cancer cells compared to cisplatin.