Synthesis, Characterization and Anticancer Potency of Copper(II) Complex of Coumarin and 4-(2-Aminoethyl)morpholine based Schiff Base

A Schiff base ligand (L) synthesized from coumarin and 4-(2-aminoethyl)morpholine and its copper(II) complex was synthesized and characterized by elemental analysis, HRMS, UV-Vis, FT-IR, NMR and EPR spectroscopy. The IR band at 3358 cm–1 correspond to the O-H stretching vibration in the free ligand was intact and shifted to 3336 cm–1 in the complex. In 1H NMR, aromatic protons of the ligand were observed at 7.96-7.26 ppm while that of morpholine and ethylene were observed at 3.71-2.63 ppm, conforming the formation of Schiff base. Similarly, 13C NMR exhibited the peaks related to the individual carbon atoms in the ligand. Formation of the proposed ligand and complex was additionally supported by the HRMS spectra. Further, molecular structure of the ligand (L) was confirmed by X-ray crystallography having orthorhombic space group P212121. The unit cell dimensions were a = 5.4258(3) Å, b = 12.4715(9) Å, c = 23.6349(16) Å. The observed g values, g|| > g⊥ > ge (g||; 2.3559 and g⊥; 2.0669) for the complex indicated the Cu(II) ion in the square planner geometry. The anticancer potency of the compounds was performed with the MCF-7 cell line. The IC50 values of the free ligand was found 256.60 ± 0.11 µg/mL and that of complex [CuLCl2], 118.50 ± 0.40 µg/mL. Cell cycle study of [CuLCl2] complex showed a higher proportion of cells in G1 (33.18%) and S (23.40%) phases and a lower proportion of cells in G2 phase (30.91%). A molecular docking study showed binding affinity of the ligand; ΔG = -7.3 kcal/mol and it’s complex with ΔG = -8.0 kcal/mol along with H-bond interaction with protein EGFR, which indicates potential interactions with the biological targets.