Introduction: 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 Ab Initio (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.

Superparamagnetic iron oxide nanoparticles have been synthesized using chain length of (3-aminopropyl) triethoxysilane for cancer therapy. First, we have developed a layer by layer functionalized with grafting 2,4‐toluene diisocyanate as a bi‐functional covalent linker onto a nano-Fe₃O₄ support. Then, they were characterized by Fourier transform infrared, X-ray powder diffraction, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, and VSM techniques. Finally, all nanoparticles with positive or negative surface charges were tested against K562 (myelogenous leukemia cancer) cell lines to demonstrate their therapeutic efficacy by MTT assay test. We found that the higher toxicity of Fe₃O₄@SiO₂@APTS ∼ Schiff base-Cu(II) (IC₅₀: 1000 μg/mL) is due to their stronger in situ degradation, with larger intracellular release of iron ions, as compared to surface passivated NPs. For first time, the molecular dynamic simulations of all compounds were carried out afterwards optimizing using MM+, Semi-empirical (AM1) and Ab-initio (STO-3G), Forcite Gemo Opt, Forcite Dynamics, Forcite Energy and CASTEP in Materials studio 2017. The energy (eV), space group, lattice parameters (Å), unit cell parameters (Å), and electron density of the predicted structures were taken from the CASTEP module of Materials Studio. The docking methods were used to predict the DNA binding affinity, ribonucleotide reductase, and topoisomerase II.

Two new mixed‐ligand complexes with general formula [Cu(SB)(L')]ClO₄ (1 and 2) were synthesized and characterized by different spectroscopic and analytical techniques including Fourier transform infrared (FT‐IR) and UV–Vis spectroscopy and elemental analyses. The SB ligand is an unsymmetrical tridentate NN'O type Schiff base ligand that was derived from the condensation of 1,2‐ethylenediamine and 5‐bromo‐2‐hydroxy‐3‐nitrobenzaldehyde. The L' ligand is pyridine in (1) and 2,2′‐dimethyl‐4,4′‐bithiazole (BTZ) in (2). Crystal structure of (2) was also obtained. The two complexes were used as anticancer agents against leukemia cancer cell line HL‐60 and showed considerable anticancer activity. The anticancer activity of these complexes was comparable with the standard drug 5‐fluorouracil (5‐FU). Molecular docking and pharmacophore studies were also performed on DNA (PDB:1BNA) and leukemia inhibitor factor (LIF) (PDB:1EMR) to further investigate the anticancer and anti‐COVID activity of these complexes. The molecular docking results against DNA revealed that (1) preferentially binds to the major groove of DNA receptor whereas (2) binds to the minor groove. Complex (2) performed better with 1EMR. The experimental and theoretical results showed good correlation. Molecular docking and pharmacophore studies were also applied to study the interactions between the synthesized complexes and SARS‐CoV‐2 virus receptor protein (PDB ID:6LU7). The results revealed that complex (2) had better interaction than (1), the free ligands (SB and BTZ), and the standard drug favipiravir.