Some new morpholine-based Schiff-base complexes; Synthesis, characterization, anticancer activities and theoretical studies

A new morpholine-based ligand (2) has been prepared from condensation of a branched amine containing morpholine, N1-(3-morpholinopropyl)-N1-((pyridine-2-yl)methyl)ethane-1,2-diamine (1), and salicylaldehyde. Metal complexes were synthesized by reaction of the ligand and metal salts in ethanol and the resulting products were characterized by elemental analyses, ESI-MS, ¹H and ¹³C NMR spectra, infrared, and UV–Vis spectroscopy. The structure of two complexes including [ZnL](ClO₄) (3) and [NiHL](ClO₄)·H₂O (6a) have been determined by single crystal X-ray structural analysis, showing that the metal atoms are in a distorted trigonal bipyramidal (Zn) and a square planar (Ni) environment, respectively. Compounds were assayed for their anticancer activities against a panel of human tumor cell lines, including breast cancer cells (MCF-7, MDA-MB-231), prostate cancer cells (PC-3) and human normal lung fibroblast cells (WI-38). Compounds 1, 2, 7, 9 and 10 demonstrated lower activity against MCF-7, MDA-MB-231 and PC-3 cell lines (IC_50s > 100 µM) compared to other compounds. It has been shown that complexes 3, 4, 5, 6, and 8 possess different anticancer potentials against MCF-7, MDA-MB-231 and PC-3. More importantly, it was observed that compounds 3, 5 and 6 demonstrate a lower activity against WI-38 normal cell line than they do against cancer cell lines. Our results indicated that compound 8 has the highest anticancer activity on cancer cell lines, and the reason for that can be attributed to the presence of a silver atom in the complex. These results clearly showed that the anticancer activities of these compounds depend on the type of metal in the complex as well as the tested cancer cell line. Furthermore, the geometries of the [ML]ⁿ⁺ (M = Zn²⁺, Cd²⁺, Mn²⁺, Cu²⁺, Ni²⁺, Ag⁺, Fe³⁺ and Co²⁺, n = 0, 1, 2) complexes have been optimized at the BP86/def2-SVP level of theory. The nature of M → L bonds in [ML]ⁿ⁺ complexes have been studied with the help of NBO analysis.