Ruthenium(II) Complexes of Isothiazole Ligands: Crystal Structure, HSA/DNA Interactions, Cytotoxic Activity and Molecular Docking Simulations

Abstract

AbstractTwo new neutral ruthenium(II) complexes [Ru(η6‐p‐cymene)Cl2(1)] (3) and [Ru(η6‐p‐cymene)Cl2(2)] (4) (1=5‐(phenylamino)‐3‐pyrrolidin‐1‐ylisothiazole‐4‐carbonitrile; 2=3‐morpholin‐4‐yl‐5‐(phenylamino)isothiazole‐4‐carbonitrile) have been synthesized and characterized using elemental analysis, IR, UV‐Vis and NMR spectroscopy. The crystal structure was confirmed for complex 3 and both ligands. Examination of the interactions of ligands and complexes with CT‐DNA (Calf Thymus DNA), as well as with HSA (Human Serum Albumin) revealed that ligands and complexes could interact with CT‐DNA through intercalation and could bind strongly with HSA. Docking experiments toward DNA dodecamer indicate excellent accordance with experimental ΔG values. The cytotoxic activity of ligands and complexes was evaluated by MTT assay against HCT116 and HeLa tumoral cells. The complexes 3 and 4 showed good activity and selectivity on HCT116 cells. Neither of the tested compounds shows cytotoxic activity against a healthy MRC‐5 cell line. Flow cytometry analysis showed the apoptotic death of the HCT116 cells with a cell cycle arrest in the S‐phase.