Ruthenium(II) Paracymene complexes of phenolic acids: Synthesis, chemical characterization, in-silico biomolecular interaction and cytotoxicity studies

Abstract

Presently, Ruthenium (Ru) complexes drawn a significant attention in medicinal chemistry researchowing to their promising anti-cancer potential. The present research dealt with design, synthesis, and chemical characterization of two ruthenium (II)-p-cymene based phenolic acid. The structural analysis revealsthat the Ru(II) complexes acquire a ‘piano stool’ coordination geometry comprises of one bound arene, two sigma bonded esteric oxygen atoms, and labile chlorine linked to Ru(II). The optical properties of these complexes were studied,which showed absorption peaks at 270 nm and 320 nm, which are due to the contribution of intra-ligand charge transitions and metal-to-ligand charge transitions, respectively. The binding interaction of the Ru(II) complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) is non-covalent in nature and the binding constants of Ru-1 and Ru-2 complexes with CT-DNA and BSA were found to be 3.6 × 10³ M⁻¹,2.5 × 10⁶ M⁻¹ and 1 × 10⁶ M⁻¹, 9.9 × 10⁴ M⁻¹respectively. It is also observed that in presence of Ru(II) complexes, ethidium bromide (EtBr) was competitively displaced from CT-DNA through intercalation, which is well supported by viscosity and in silico studies. The cytotoxicity study of these Ru(II) complexes was conducted with multiple cancer cell lines (HeLa, MDA-MB-231, MCF-7, Hep G2) and one human embryonic kidney cell (HEK-293). Both Ru(II) complexes were investigated in-vitro for cytotoxicity against HeLa, MCF-7, Hep G2 and MDA-MB-231 cells. The obtained results show that Ru-1 and Ru-2 (ranging from 2.5 to 8.4 μM) exhibits considerable potency and selectivity towards cancer cell lines in compare to cisplatin.