Organometallic ruthenium(II) scorpionate as topo IIα inhibitor; in vitro binding studies with DNA, HPLC analysis and its anticancer activity

New organoruthenium [(eta(6)-arene)Ru-II(L)Cl]Cl (1: arene = p-cymene, L = L-1; 2: arene = p-cymene, L = L-2; 3: arene = benzene, L = L-1; 4: arene = benzene; L = L-2; L-1 = bis(3,5-dimethylpyrazolyl)parabenzoic acid, L-2 = bis(3,5-dimethylpyrazolyl)metabenzoic acid) have been synthesized and characterized by analytical and spectroscopic methods. The molecular structure of [(eta(6)-p-cymene)RuCl(L-1)]Cl (1) was determined by single crystal X-ray diffraction studies. Preliminary in vitro binding studies of 1-4 with CT DNA were carried out by employing various biophysical techniques which revealed their avid DNA binding via non-covalent binding mode viz; partial intercalation of the eta(6)-arene group as well as electrostatic surface interaction through one oxygen atom of the phosphate backbone of the DNA helix; however, complexes 1 and 3 display higher binding propensity in comparison to 2 and 4, as quantified by K-b. The interaction was further analysed by HPLC technique. The results of the cleavage experiments of pBR322 DNA with 1 and 3 displayed significantly good cleavage at 20-40 mu M, following the oxidative pathway. These findings have revealed that the hydrophobic arene, and the chloride leaving group have important roles in the novel mechanism of recognition of DNA by (eta(6)-arene)ruthenium(II) complexes, and will aid the design of more effective anticancer complexes, as well as new site-specific DNA reagents. Furthermore, the anticancer activity of the complexes 1 and 3 on 15 cell lines of different histological origin has been studied. It has been observed that I exhibits higher cytotoxicity than 3, and the cells undergo apoptotic cell death.