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

Abstract

The two novel Cu(II) complexes [Cu(L)(CH 3 COO)] 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.

Biological Activity of Two Anticancer Pt Complexes with a Cyclohexylglycine Ligand against a Colon Cancer Cell Line: Theoretical and Experimental Study

“…Schematic molecular models of the complexes are shown on the right side of Figure . The decrease in intensity across both positive and negative bands, with no red or blue shift for 1 and a slight blue shift of the positive band centered at around 275 nm for 2 , and the weak interaction of the free ligands of HL and bipy can be observed, clearly showing that drug binding to B-DNA creates conformational changes, such as the opening of the helix, and suggest that the electrostatic approach and groove binding may be merged. − …”

DNA/HSA binding and anticancer properties of pendant acetate bearing mono-nuclear Ni(ii) and bridging acetate bearing di-nuclear Cu(ii) Schiff base complexes: an experimental and molecular docking study

“…Although there is no established correlation between the DNA binding ability of a complex and its anticancer efficacy, scattered literature reports indicate that in many cases a complex with potential DNA binding efficacy exhibits better anticancer properties. 58–61 Thinking in the same line, we can also propose that compound 2 's superior DNA binding efficiency is responsible for its improved anticancer properties.…”

“…The docking study was carried out using MOE.2009 software. 13,43,55 DNA and HSA crystal data (6elb.pdb and 2bxd.pdb, respectively) were downloaded from pdb and these data were used for docking studies. The probable binding sites in each macromolecule were identified using a site finder.…”

“…[3][4][5] As an alternative for platinum metal complexes showing potential anticancer properties, Cu complexes and a few Ni complexes are important among numerous 3d transition metal complexes. [6][7][8][9][10][11][12][13][14] The primary rationale for placing a special emphasis on the Cu complexes in the field of anticancer drug development research is that cancer cells react differently to Cu complexes than normal cells do. Furthermore, they play a significant role in a number of cellular processes and are essential for angiogenesis, a process essential for tumor growth, invasion, and metastasis.…”

DNA/Protein Binding and Apoptotic-Induced Anticancer Property of a First Time Reported Quercetin–Iron(III) Complex Having a Secondary Anionic Residue: A Combined Experimental and Theoretical Approach

“…The innermetallic complexes have generally been formed in the majority of situations. However, even though it is well established that a secondary anionic residue plays a significant role in the demonstration of effective anticancer property, no report has been found in which metal–quercetin complexes have been developed bearing secondary anionic residues to examine their anticancer properties. − The metal complex’s anticancer property can be managed by carefully choosing the metal ion. Fe complexes occupy a prominent position among the many nonplatinum metal complexes.…”