A study of the synthesis, characterization, cytotoxicity assessment, and molecular docking of Cu(II), Ni(II), and Co(II) ions with Schiff base and 1,10-phenanthroline

This work covers the synthesis, cytotoxicity evaluation, and molecular docking study of new metal complexes formed by the coupling of 2-(((2-hydroxyphenyl)imino)methyl)-4-nitrophenol (L1) and 1,10-phenanthroline (L2) ligands. The ligand (L1) and its mixed ligand complexes with Cu(II), Co(II), and Ni(II) salts were analyzed using elemental analysis, FT-IR, TGA, UV-Vis, LC-MS/MS, NMR (just for the ligand L1), and magnetic susceptibility assessments. To our knowledge, this is the first report evaluating the cytotoxic and apoptotic effects of these complexes on A549 lung carcinoma and SH-SY5Y neuroblastoma cells. Among all synthesized compounds, copper complexes ([Cu(L1)(L2)H₂O] and [Cu(L1)2(H₂O)2]) exhibited significant cytotoxicity with IC50 values of 14.18 µM and 5.17 µM in A549 cells, and 37.96 µM and 23.35 µM in SH-SY5Y cells, respectively. Annexin V/PI apoptosis assays confirmed that the copper complexes induced both early and late apoptosis more effectively than cisplatin in A549 cells. Molecular docking studies further validated these findings, revealing strong interactions of copper complexes with B-DNA, EGFR, VEGFR-2, and ERK2, consistent with the observed anticancer activities. These results suggest that Cu(II)–Schiff base complexes represent promising lead compounds for future anticancer drug development. © 2025 Elsevier B.V.