Dataset Information

Synthesis and toxicity assessment of Fe₃O₄ NPs grafted by ∼ NH₂-Schiff base as anticancer drug: modeling and proposed molecular mechanism through docking and molecular dynamic simulation.

ABSTRACT: 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.

SUBMITTER: Eshaghi Malekshah R

PROVIDER: S-EPMC7470030 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:In this study, four new Mn(II), Fe(III), and Cr(III) complexes with two Schiff base ligands namely, 4-bromo-2-[(E)-{[4-(2-hydroxyethyl)phenyl]imino}methyl]phenol (HL1) and 2-[(E)-{[4-(2-hydroxyethyl)phenyl]imino}methyl]-4-methoxy phenol (HL2) have been synthesized and characterized. Different analytical and spectral methods have been used to characterize the ligands and their complexes. General formulas of [M(L)Cl2(H2O)2] for FeL1, CrL1 and CrL2, and [M(L)Cl(H2O)3] for MnL2 were proposed. HOMO and LUMO energies, as well as the electrical characteristics, have been calculated using DFT/B3LYP calculations with Gaussian 09 program. The optimized lowest energy configurations of the complexes are proven. The disc diffusion technique was used to test the pharmacological activities' antibacterial efficacy against diverse bacterial and fungus species. The MTT technique was used to assess the in vitro cytotoxicity of the ligands and their metal complexes on the Hep-G2 human liver carcinoma cell line and the MCF-7 human breast cancer cell line. All compounds displayed better activity compared to the free ligands. MnL2 complex showed predominant activity when compared to the other complexes with an IC50 value of 2.6 ± 0.11 μg/ml against Hep-G2, and against MCF-7 the IC50 value was 3.0 ± 0.2 μg/ml which is less than the standard drug cisplatin (4.0 μg/ml). UV-vis electronic spectrum and gel electrophoresis techniques have been used to investigate the compounds' affinity to bind and cleavage CT-DNA. The interaction's binding constants, or Kb, have been identified, and it was discovered that the new complexes' binding affinities are in the order of FeL1 > MnL2 > CrL2 > CrL1, and the binding mechanism has been suggested. To assess the kind of binding and binding affinity of the investigated drugs with human DNA, a molecular docking study was carried out (PDB:1bna). The acquired results supported the intercalation binding mechanism proposed in the experimental part and revealed that complexes may be inserted into the DNA molecule to stop DNA replication. According to ADMET data, the synthesized compounds have a high bioavailability profile and their physicochemical and pharmacological features remained within Lipinski's RO5 predicted limitations.

Dataset Information

Synthesis and toxicity assessment of Fe₃O₄ NPs grafted by ∼ NH₂-Schiff base as anticancer drug: modeling and proposed molecular mechanism through docking and molecular dynamic simulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Synthesis and toxicity assessment of Fe3O4 NPs grafted by ∼ NH2-Schiff base as anticancer drug: modeling and proposed molecular mechanism through docking and molecular dynamic simulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Synthesis and toxicity assessment of Fe₃O₄ NPs grafted by ∼ NH₂-Schiff base as anticancer drug: modeling and proposed molecular mechanism through docking and molecular dynamic simulation.