Developing a biopolymeric chitosan supported Schiff-base and Cu(II), Ni(II) and Zn(II) complexes and biological evaluation as pro-drug

Chitosan derivatives are widely used as key classes of medicinal compounds owing to their non- toxic and biodegradable properties. So, in this work, to enhance chitosan biological activities, a new synthesis of a series of Schiff base and its metals complexes (Cu(II), Ni(II) and Zn(II)) of chitosan (CS) was prepared. Moreover, their physicochemical properties were characterized by IR, UV–Vis, SEM, melting point, thermo gravimetric analysis (TGA), X-ray diffraction (XRD), elemental analysis and 1H NMR techniques. Elemental analysis data confirmed the formation of chitosan-Schiff base as well as the coordination reaction with metals ions by increasing the carbon content caused by substitution. By elemental analysis, the degrees of acetylation (DA), deacetylation (DD) and substitution (DS) were acquired 23, 77.63 and 57.90%, respectively. Additionally, the 1H NMR spectroscopy was used for the determination of degree of deacetylation (DD) and Substitution (DS) of chitosan ranging from 87.5 and 85%, respectively. The presence of a new low-field signal at 10.23 ppm in the 1H NMR spectra confirmed the imine proton of Schiff base. The cytotoxicity of Chitosan, Chitosan-Schiff base and its metals complexes was tested against K562 chronic myelogenous leukemia (CML) and MG-63 (osteosarcoma cancer) cell lines by the MTT assay. The results suggested that the anticancer activity of Schiff base and their complexes was much better than that of pure CS against cancer MG63 cell line. Finally, through flow cytometry, we demonstrated that all compounds were efficient in inducing apoptosis effect in K562 and MG63 cell lines except Schiff base- chitosan in K562 cell lines.