Synthesis, Characterization, Biomedical Application, Molecular Dynamic Simulation and Molecular Docking of Schiff Base Complex of Cu(II) Supported on Fe3O4/SiO2/APTS

Rahime Eshaghi Malekshah,1 Bahareh Fahimirad,1 Ali Khaleghian2 1Department of Chemistry, College of Science, Semnan University, Semnan, Iran; 2Biochemistry Department, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, IranCorrespondence: Ali KhaleghianDepartment of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, 5th Km Damghan Road, P.O. Box 3514533, Semnan 3513138111, IranFax +98 2333654202Email khaleghian.ali@gmail.comIntroduction: Over the past several years, nano-based therapeutics were an effective cancer drug candidate in order to overcome the persistence of deadliest diseases and prevalence of multiple drug resistance (MDR).Methods: The main objective of our program was to design organosilane-modified Fe3O4/SiO2/APTS(∼NH2) core magnetic nanocomposites with functionalized copper-Schiff base complex through the use of (3-aminopropyl)triethoxysilane linker as chemotherapeutics to cancer cells. The nanoparticles were characterized by Fourier transform infrared spectroscopy(FT-IR), X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), TEM, and vibrating sample magnetometer (VSM) techniques. All analyses corroborated the successful synthesis of the nanoparticles. In the second step, all compounds of magnetic nanoparticles were validated as antitumor drugs through the conventional MTT assay against K562 (myelogenous leukemia cancer) and apoptosis study by Annexin V/PI and AO/EB. The molecular dynamic simulations of nanoparticles were further carried out; afterwards, the optimization was performed using MM+, semi-empirical (AM1) and AbInitio (STO-3G), ForciteGemo Opt, Forcite Dynamics, Forcite Energy and CASTEP in Materials studio 2017.Results: The results showed that the anti-cancer activity was barely reduced after modifying the surface of the Fe3O4/SiO2/APTS nanoparticles with 2-hydroxy-3-methoxybenzaldehyde as Schiff base and then Cu(II) complex. The apoptosis study by Annexin V/PI and AO/EB stained cell nuclei was performed that apoptosis percentage of the nanoparticles increased upon increasing the thickness of Fe3O4 shell on the magnetite core. The docking studies of the synthesized compounds were conducted towards the DNA and Topoisomerase II via AutoDock 1.5.6 (The Scripps Research Institute, La Jolla, CA, USA).Conclusion: Results of biology activities and computational modeling demonstrate that nanoparticles were targeted drug delivery system in cancer treatment.Keywords: superparamagnetic, Schiff base, core–shell, MTT assay, apoptosis, molecular docking, computational methods, Topoisomerase II