A dinuclear copper(II) complex with piperazine bridge ligand as a potential anticancer agent: DFT computation and biological evaluation

New dinuclear complex [Cu-2(bpy)(2)(im)(2)(pip)(NO3)(2)]center dot 2NO(3), 1 was synthesized and characterized by elemental analysis and various spectroscopic methods (IR, H-1 and C-13 NMR, EPR, UV-Vis, ESI-MS and XRPD). Calculation based on Density functional theory (DFT), have been performed to obtain optimized structure, harmonic frequencies, IR intensities and energies of Frontier molecular orbitals. In vitro DNA binding studies of complex 1 were carried out by employing UV-Vis, fluorescence titrations, isothermal titration calorimetry and circular dichroism that ascertained the strong electrostatic binding interaction of the complex via phosphate backbone of DNA helix as well as partial intercalation. To gain further insight into the molecular recognition toward the target site, interaction studies of complex 1 with 5'-GMP were carried out by UV-Vis titration which revealed higher propensity of 1 towards N7 of guanine base-5'-GMP. The DNA cleavage pattern revealed groove binding affinity of the complex 1 towards DNA and suggestive of hydrolytic pathway for the cleavage of pBR322 DNA. The FRET studies at room temperature also confirmed binding of the complex 1 to the CT-DNA. Furthermore, the cytotoxicity of complex 1 was examined on a panel of human tumor cell lines of different histological origins showing significant GI(50) values specifically towards MCF7, K562 and A2780 tumor cell lines, Moreover, complex 1 was assayed for telomerase inhibition using the TRAP-PCR-ELISA assay. The results showed complex 1 possessed the most potent telomerase activity (IC50 = 17.1 mu M) as well as significant SOD mimics (IC50 similar to 0.28 mu M). (C) 2016 Elsevier B.V. All rights reserved.