Development of DNA intercalative, HSA binder pyridine-based novel Schiff base Cu(II), Ni(II) complexes with effective anticancer property: A combined experimental and theoretical approach

The two novel Cu(II) complexes [Cu(L)(CH3COO)] and [Cu(L)(N-3)] (1, 2) and one Ni(II) complex [Ni(L)(N)(3)] (3) have been developed by using the ligand HL, obtained by the condensation of 2 amino methyl pyridine and 5-bromo salicylaldehyde. All the three complexes are spectroscopically characterized along with molar conductance measurement. With the help of EPR, density functional theory (DFT) studies, the occupants of distorted square planer geometry with azide (2 and 3), acetate (1) as a secondary anionic residue, and the presence of +2 oxidation state on metal center of the complexes have been documented. After structural determination, all the complexes have been exposed to inspect their DNA and human serum albumin (HSA) binding efficacy. Initially, the higher binding constants, obtained from electronic titration among complexes and DNA, the impressive reduction of fluorescence intensities of the HSA and Ethidium Bromide (EtBr)-DNA adduct, after incremental addition of complexes separately, assure the high binding ability of complexes 2 and 3 in compare with 1. The time-dependent fluorescence study, isothermal titration calorimetry (ITC), and circular dichroism (CD) spectral titration provide the additional support to get affirmation about the binding potentiality of the aforementioned complexes with DNA/HSA. The molecular docking study authenticates the experimental approach. Furthermore, the anticancer study of all the complexes has been checked by implementing the MTT assay method on two cancer cell lines and one normal cell line. The MTT assay results explore the better anticancer property of complex 2 in comparison with complexes 1 and 3 with low toxicity to the normal cell, and this fact may be correlated with the impressive DNA and HSA binding efficacy of complex 2. Finally, the nuclear staining study by AO/PI dual sensor discloses the nuclear morphological change of cancer cells along with the opening of cell death mechanism, suggesting the apoptotic pathway.

Automated summary

Two novel Cu(II) complexes and one Ni(II) complex have been developed and characterized for their structure and properties, including their binding ability with DNA and human serum albumin. Experimental methods and molecular docking studies confirmed the binding potential of these complexes with DNA and HSA, as well as their anticancer properties. The nuclear staining study revealed the nuclear morphological changes in cancer cells and suggested the activation of apoptotic pathways.