Biological evaluation, proposed molecular mechanism through docking and molecular dynamic simulation of derivatives of chitosan.

We synthesized Schiff base and its complexes derivatives of chitosan (CS) in order to develop antibiotic compounds based on functionalized-chitosan against gram-positive and gram-negative bacteria. IR, UV-Vis, AFM, SEM, Melting point, X-ray diffraction (XRD), elemental analysis, and 1H NMR techniques were employed to characterize the chemical structures and properties of these compounds. XRD, UV-Vis, and 1H NMR techniques confirmed the formation of Schiff base and its functionalized-chitosan to metals. Subsequently, our antibacterial studies revealed that antibacterial activities of [Zn(Schiff base)(CS)] against S. aureus bacteria increased compared to those of their compounds. In addition, hemolysis test of CS-Schiff base-Cu(II) demonstrated better hemolytic activity than vitamin C, CS-Schiff base, CS-Schiff base-Zn(II), and CS-Schiff base-Ni(II). In a computational strategy, we carried out the optimization of compounds with molecular mechanics (MM+), Semi-emprical (AM1), Abinitio (STO-3G), AMBER, BIO+(CHARMM), and OPLS. Frontier orbital density distributions (HOMO and LUMO), and the optimized computational UV of the compounds were assessed. The optimized computational UV-Vis was similar to the experimental UV-Vis. We applied the docking methods to predict the DNA binding affinity, Staphylococcus aureus enoyl-acyl carrier protein reductase (ENRs), and Staphylococcus aureus enoyl-acyl carrier protein reductase (saFabI). Ultimately, the obtained data herein suggested that Schiff base is more selective toward ENRs and saFabI compared to chitosan, its complexes, and metronidazole.

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.