Design, synthesis, DNA-binding affinity, cytotoxicity, apoptosis, and cell cycle arrest of Ru(II) polypyridyl complexes

摘要

A novel polypyridyl ligand CNPFIP (CNPFIP = 2-(5(4-chloro-2-nitrophenyl)furan-2-yl)-1H-imidazo[4,5f] [1,10]phenanthroline) and its mononuclear Ru(II) polypyridyl complexes of [Ru(phen)(2)CNPFIP](2+) (1) (phen = 1,10-phenanthroline), [Ru(bpy)(2)CNPFIP](2+) (2) (bpy = 2,2'-bipyridine), and [Ru(dmb)(2)CNPFIP](2+) (3) (dmb = 4,4'-dimethyl-2,2'-bipyridine) have been synthesized successfully and characterized thoroughly by elemental analysis, UV/Vis, IR, NMR, and ESI-MS. The interaction of the Ru(II) complexes with calf thymus DNA (CT-DNA) was investigated by absorption titration, fluorescence, viscosity measurements. The experimental results suggest that three complexes bind to CT-DNA through an intercalative mode and the DNA-binding affinity of complex 1 is greater than that of complexes 2 and 3. The photo-cleavage of plasmid pBR322 DNA by ruthenium complexes 1, 2, and 3 was investigated. We have also tested three complexes for their antimicrobial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria. The in vitro cytotoxicity of these complexes was evaluated by MTT assay, and complex 1 shows higher cytotoxicity than 2 and 3 on HeLa cells. The induced apoptosis and cell cycle arrest of HeLa cells were investigated by flow cytometry for 24 h. The molecular docking of ruthenium complexes 1, 2, and 3 with the active site pocket residues of human DNA TOP1 was performed using LibDock. (C) 2015 Elsevier Inc. All rights reserved.