Schiff Bases Ligands Derived from o-Phthalaldehyde and Their Metal Complexes with Cu2+ and Ni2+: Synthesis, Anti-Breast Cancer and Molecular Docking Study

Abstract

The Schiff bases and their complexes have an observed biological efficacy, so in the current study it has been prepared, characterized and evaluated the biological activity of some Schiff bases and their metal complexes with copper and nickel and based on ortho-phathaldehyde as a primary compound. A new Schiff bases ligands and metal complexes {[Cu(L)n(H2O)2]Cl2.mH2O and [Ni(L)n].mH2O, where L=N',N'''-((1E,1'E)-1,2-phenylenebis(methanylylidene)) di(benzohydrazide) L1, N',N'''-((1E,1'E)-1,2-phenylenebis (methanylylidene)) di(isonicotinohydrazide) L2, 1,2-bis((E)-(2-(2,4,6-trichlorophenyl)hydrazono)methyl) benzene L3 ; n = 1, 2 ; m = 0, 1, 3/2, 5/2} have been synthesized and elucidated by mass, FT-IR, 13C and 1HNMR, molar conductivity, flame-atomic absorption, magnetic susceptibility, Powder-XRD and TG analysis. The results showed that the L1 and L2 ligands behave as a tetra-dentate donor and were associated with metal ions in a molar ratio of 1:1, while L3 ligand was bi-dentate donor and associated with metal ions in 1:2 molar ratio. In addition, the geometric shapes of the prepared complexes were tetrahedral and square planar for Ni2+ and Zn2+ complexes, and octahedral for Cu2+ complexes. The effect of cellular toxicity in the laboratory has been examined by MTT assay for all compounds against the MCF-7 cancer breast cell line and found to have low efficacy except [Cu(L3)2(H2O)2] Cl2.H2O (5). The copper complex's molecular docking has been performed with breast cancer proteins using the MOE program, and found to target ERα, CDK6 and EGFR proteins by binding to hydrogen bonds and pi-interactions. HIGHLIGHTS Synthesis new chemical compounds, which are some Schiff bases and their metal complexes with copper and nickel ions Characterization of chemical structure of synthesized compounds by mass, FT-IR, 13C and 1HNMR, molar conductivity, flame-atomic absorption, magnetic susceptibility, Powder-XRD and TG analysis Study the biological activity of synthesized compounds as anti-breast cancer Study of molecular docking of compounds that showed biological efficacy with proteins responsible for breast cancer cells GRAPHICAL ABSTRACT