Studies of Ruthenium(II) based complexes against cancer

Abstract

Recently in the field of chemotherapeutics to combat the side effects of cisplatin, ruthenium complexes are being investigated extensively. In this work, a bidentate benzimidazole based ligand, HL [HL=2-(1H benzo[d]imidazol-2-yl)-6-methoxyphenol] was utilized to obtain three Ru(II) arene complexes having a generalized formula [Ru(K6 -p cym)(L)(X)] (where p-cym = p-cymene, X = Cl) and [Ru(K6 -p cym)(L)(X)]PF6 (where p-cym = p-cymene, X = (i) PPh3 = triphenyl phosphine, (ii) PTA = 1,3,5-triaza-7-phosphaadamantane) to explore their prospective anticancer activities. All of the synthesized compounds were characterized thoroughly using different analytical techniques including MS, NMR, FTIR, UV-Vis and fluorescence spectroscopy. A stability study using UV spectroscopy confirmed that the complexes remained stable in biological medium. It was also observed that both the ligand and the complexes are fluorescent in nature. A fluorescence quenching experiment with serum albumin proteins revealed that there is good interaction between the complexes and HSA (Human Serum Albumin) and BSA (Bovine Serum Albumin). The applications of the synthesized compounds were further explored by conducting a DNA binding study using absorption spectroscopy and fluorometric titration with DAPI ( ¶ - Diamidino-2-Phenylindole) to check whether the compound interacts with the DNA via groove binding. The complexes were additionally checked for their lipophilic nature and found to be catalyzing the transfer of hydrogen from NADH to get it converted into (Nicotinamide Adenine Dinucleotide) NAD+ , thus inducing oxidative stress. An MTT Assay revealed the extent of cytotoxicity of the compounds against different tumor cell lines. Furthermore, Hoechst staining indicated the ability of the complexes to bring about apoptosis in cancer cells.