In vitro studies on the selective cytotoxic effect of luminescent Ru(ii)-p-cymene complexes of imidazo-pyridine and imidazo quinoline ligands

Abstract

In recent years, Ru(II) complexes have gained high importance in medicinal chemistry due to their significant anti-cancer activities, which are directly related to their DNA binding ability. In this report, the chemistry and cytotoxicity of two new Ru(II) complexes containing imidazole pyridine (Ru-1) and imidazole quinoline (Ru-2) have been studied. The prepared compounds were characterized using infrared (IR), nuclear magnetic resonance (NMR), mass spectrometry (MS), isothermal titration calorimetry (ITC), UV-Vis, and fluorescence spectral techniques. The structural analyses show that the Ru(II) complexes exhibit a ‘piano stool’ coordination geometry and they are composed of one bound arene, two sigma bonded benzil nitrogen atoms, and labile chlorine linked to Ru(II). The photo-physical properties of these complexes were examined, and they exhibit absorption peaks at 260 nm and 380 nm, which are due to the involvement of intra-ligand charge transitions (ILCT) and metal-to-ligand charge transitions (MLCT), respectively. The binding process of the Ru(II) complexes with DNA and BSA is non-covalent in nature and the binding constants of Ru-1 and Ru-2 complexes with DNA and BSA were found to be 1 × 10⁵ M⁻¹ and 1 × 10³ M⁻¹, respectively. In the presence of the Ru(II) complexes, ethidium bromide (EtBr) is competitively displaced from DNA by intercalation of the Ru(II) complexes in DNA and it is well corroborated by viscosity and in silico studies. Both the ligands and Ru(II) complexes were carefully investigated in vitro for cytotoxicity against HeLa, MCF-7, and MDA-MB-231 cells. Surprisingly, both Ru(II) complexes exhibit superior cytotoxicity to cisplatin with a low LD₅₀ value against the examined cancer cells. Besides, an insignificant effect on HEK normal cells (LD₅₀ > 140 μM) was observed.