DNA cleavage activity and cytotoxicity of mononuclear and trinuclear Cu(II) complexes containing 1H-pyrazole-3,5-dicarboxylic acid as ligand

UV-vis titrations of complexes [Cu(H2pdc)2(H2O)2] (1) and [Cu3(pdc)2(bpy)2(H2O)4] (2) (H3pdc=1H-pyrazole3,5-dicarboxylic acid, bpy=2,2' bipyridine) with calf thymus DNA demonstrate their moderate binding with DNA. Fluorescence titrations show significant displacement of ethidium bromide bound to DNA by the complexes. Agarose gel electrophoretic mobility assay indicates that the complexes are able to cause concentration-dependent nicking of supercoiled DNA under physiological conditions. Ligation experiments with T4 DNA ligase enzyme show that the nicked DNA cleavage products generated by complexes (1) and (2) is religated to a large extent in the presence of T4 ligase enzyme. Complex (2) shows potential cytotoxicity against CaSki cervical cancer, HL-60 leukemic cell lines and THP-1 human monocytic cell lines with IC50 value of 1.5 μM, 2.5 μM and 10 μM respectively. A redox inactive Zn(II) complex of type [Zn(H2pdc)2(H2O)2]· H2O (3) was also synthesized and characterized but owing to its poor solubility, further studies could not be carried out.