Dissymmetric thiosemicarbazone ligands containing substituted aldehyde arm and their ruthenium(II) carbonyl complexes with PPh_3/AsPh_3 as ancillary ligands: Synthesis, structural characterization, DNA/BSA interaction and in vitro anticancer activity

摘要

A serious of new dissymmetric ruthenium(II) carbonyl complexes of the type [Ru(CO)(EPh_3)(L1-2)] (1-4), [E = P or As; L1 = N~4-(2-Hydroxy-5-chlorobenzylidene)-2-amino-5-chlorobenzophenone thiosemicarbazone; L2 = N~4-(2-Hydroxynaphthalene-1-carbaldehyde)-2-amino-5-chlorobenzophenone thiosemicarbazone] have been synthesized and characterized by several spectroscopic studies. The molecular structure of the ligand L1 and the ruthenium(II) carbonyl complexes (2, 4) have been analyzed by single crystal X-ray studies, and found that the ruthenium(II) complexes possess a distorted octahedral geometry. The DNA binding studies such as emissive titration, Ethidium bromide/Methylene blue (EB/MB) displacement assay and viscometry measurements revealed that the ruthenium(II) complexes bound with calf thymus DNA through intercalative mode with relatively high binding constant values. Further, the interactions of the complexes with bovine serum albumin (BSA) were also investigated using fluorescence spectroscopic methods, which showed that the new complexes could bind strongly with BSA. The complexes (1-4) were tested for DNA and BSA cleavage activities, and the results showed that the complexes exhibited good cleavage properties. In addition, the newly synthesized ruthenium(II) complexes possess better in vitro cytotoxic activities against various cell lines (MCF-7, Hop62, MDA-MB- 435) and AO/EB staining method showed that these complexes induced apoptosis of MCF-7 cell lines.