Multi-stage screening to predict the specific anticancer activity of Ni(II) mixed-ligand complex on gastric cancer cells; biological activity, FTIR spectrum, DNA binding behavior and simulation studies

[Display omitted] •Anti-cancer activity of novel synthesized Ni(II) complex was investigated on gastric cancer cells.•The applications of FTIR spectroscopy to target identification in chemotherapy was discussed.•The UV–Vis spectroscopy showed that the complex was able to bind with DNA via groove, non-covalent, and electrostatic interactions.•The interaction between DNA and Ni(II) complex was examined in detail by docking and NCI analysis at the M062X/6-311++G** level of theory.•A 400 ns MD simulation was performed against DNA and Ni(II) complex system of the docking output. The anticancer activity of a transition metal complex with [Ni(L1)2L2]H2O (where L1 and L2 were acetylacetonato (acac) and 2-aminopyridine (2-ampy), respectively) was evaluated in MKN45 cell line. Methyl thiazolyl tetrazolium (MTT) assay was performed to assess the antitumor capacity of the Ni(II) complex against gastric cancer cell line MKN45. The complexexhibited high in vitro antitumor activity against MKN45 cells with IC50values of 1.99 μM in 48 hrs. The alterations in the structure of cellular biomolecules (proteins, lipids, carbohydrates, and especially DNA) by the Ni(II) complex were confirmed by bio spectroscopic studies. Fourier Transformed Infrared (FTIR) spectroscopy analysis revealed significant differences between untreated and treated MKN45 cell line in the region of glycogen, nucleic acid, amide I and amide II bands (1000, 1100, ~1650, and ~1577 cm−1). The absorption bands 1150 cm−1 and 1020–1025 cm−1 can be assigned to the CO bond of glycogen and other carbohydrates and are significantly overlapped by DNA. The interaction of calf thymus (CT) DNA with Ni(II) complex was explored using absorption spectral method. The UV–visible studies demonstrated that this complex was able to bind with DNA via groove, non-covalent, and electrostatic interactions, and binding constant (Kb) was found to be 3 * 104. Docking simulation and Non Covalent Interaction (NCI) topological analysis were conducted to provide insights into the nature of DNA/complex interactions. The binding affinity and binding stability of complex was validated by 400-ns MD simulations.