Search

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 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.Keywords: superparamagnetic, Schiff base, core–shell, MTT assay, apoptosis, molecular docking, computational methods, Topoisomerase II

The present study uses molecular docking and dynamic simulations to evaluate the inhibitory effect of flavonoid glycosides-based compounds on coronavirus Main protease (M pro ) and RNA polymerase. The Molegro Virtual Docker (MVD) software is utilized to simulate and calculate the binding parameters of compounds with coronavirus. The docking results show that the selected herbal compounds are more effective than those of chemical compounds. It is also revealed that five herbal ligands and two chemical ligands have the best docking scores. Furthermore, a Molecular Dynamics (MD) simulation was conducted for Hesperidin, confirming docking results. Analysis based on different parameters such as Root-mean-square deviation (RMSD), Root mean square fluctuation (RMSF), Radius of gyration (Rg), Solvent accessibility surface area (SASA), and the total number of hydrogen bonds suggests that Hesperidin formed a stable complex with M pro . Absorption, Distribution, Metabolism, Excretion, And Toxicity (ADMET) analysis was performed to compare Hesperidin and Grazoprevir as potential antiviral medicines, evaluating both herbal and chemical ligand results. According to the study, herbal compounds could be effective on coronavirus and are admissible candidates for developing potential operative anti-viral medicines. Hesperidin was found to be the most acceptable interaction. Grazoprevir is an encouraging candidate for drug development and clinical trials, with the potential to become a highly effective M pro inhibitor. Compared to RNA polymerase, M pro showed a greater affinity for bonding with Hesperidin. van der Waals and electrostatic energies dominated, creating a stable Hesperidin-M pro and Hesperidin-RNA polymerase complex., Competing Interests: The authors report there are no competing interests to declare., (© 2024 Published by Elsevier B.V.)

Hydrogels based on chitosan or alginate biopolymers are believed to be desirable for covering skin lesions. In this research, we explored the potential of a new composite hydrogels series of sodium alginate (Alg) filled with cross-linked chitosan to use as hydrogel wound dressings. Cross-linked chitosan (CSPN) was synthesized by Schiff-base reaction with aldehydated cyclophosphazene, and its Cu(II) complex was manufactured and identified. Then, their powder suspension and Alg were transformed into hydrogel via ion-crosslinking with Ca 2+ . The hydrogel constituents were investigated by using FTIR, XRD, rheological techniques, and thermal analysis including TGA (DTG) and DSC. Moreover, structure optimization calculations were performed with the Material Studio 2017 program based on DFT-D per Dmol 3 module. Examination of Alg's interactions with CSPN and CSPN-Cu using this module demonstrated that Alg molecules can be well adsorbed to the particle's surface. By changing the dosage of CSPN and CSPN-Cu, the number and size of pores, swelling rate, degradation behavior, protein absorption rate, cytotoxicity and blood compatibility were changed significantly. Subsequently, we employed erythromycin as a model drug to assess the entrapment efficiency, loading capacity, and drug release rate. FITC staining was selected to verify the hydrogels' intracellular uptake. Assuring the cytocompatibility of Alg-based hydrogels was approved by assessing the survival rate of fibroblast cells using MTT assay. However, the presence of Cu(II) in the developed hydrogels caused a significant antibacterial effect, which was comparable to the antibiotic-containing hydrogels. Our findings predict these porous, biodegradable, and mechanically stable hydrogels potentially have a promising future in the wound healing as antibiotic-free antibacterial dressings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The computational analysis of drug release from metal-organic frameworks (MOFs), specifically UiO-66, is the primary focus of this research. MOFs are recognized as nanocarriers due to their crystalline structure, porosity, and potential for added functionalities. The research examines the release patterns of three drugs: temozolomide, alendronate, and 5-fluorouracil, assessing various factors such as the drugs' distance from the UiO-66 centers, the interaction of drug functional groups with Zr metal ions, and the drug density throughout the nanocarrier. Findings reveal that 5-fluorouracil is located furthest from the UiO-66 center and exhibits the highest positive energy compared to the other drugs. Alendronate's density is observed to shift to the carrier surface, while 5-fluorouracil's density significantly decreases within the system. The drug density diminishes as the distance from the UiO-66 center of mass increases, suggesting a stronger positive interaction between the drugs and the nanocarrier. Moreover, Monte Carlo calculations were employed to load drugs onto the UiO-66 surface, leading to a substantial release of 5-fluorouracil from UiO-66. Quantum and Monte Carlo adsorption localization calculations were also conducted to gather data on the compounds' energy and geometry. This research underscores the potential of MOFs as nanocarriers for drug delivery and highlights the crucial role of temperature in regulating drug release from UiO-66. It provides insights into the complex dynamics of drug release and the factors influencing it, thereby emphasizing the promise of UiO-66 as a viable candidate for drug delivery. This work contributes to our understanding of UiO-66's role and sets the stage for improved performance optimization in the cancer treatment., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This study delves into the interaction between benzodiazepine (BZD) drugs and 2-hydroxypropyl-β-cyclodextrin (2HPβCD), a cyclodextrin (CD) known to improve drug delivery and enhance therapeutic outcomes. We find that the 2HPβCD's atoms become more rigid in the presence of chlordiazepoxide (CDP), clonazepam (CLZ), and diazepam (DZM), whereas they become more flexible in the presence of nordazepam (NDM) and nitrazepam (NZP). We also investigated the structure of 2HPβCD and found that loading these drugs increases both the area and volume of the 2HPβCD cavity, making it more suitable for drug delivery. Moreover, this research found that all drugs exhibited negative values for the binding free energy, indicating thermodynamic favorability and improved solubility. The binding free energy order of the BZDs was consistent in both molecular dynamics and Monte Carlo methods, with CDP and DZM having the highest affinity for binding. We also analyzed the contribution of different interaction energies in binding between the carrier and the drugs and found that Van der Waals energy is the primary component. Our results indicate that the number of hydrogen bonds between 2HPβCD/water slightly decreases in the presence of BZDs, but the hydrogen bond's quality remains constant., (© 2023. The Author(s).)

The present study aimed to synthesis a proper scaffold consisting of hydroxylated polyphosphazene and polycaprolactone (PCL), focusing on its potential use in tissue engineering applications. The first grafting of PCL to poly(propylene glycol)phosphazene (PPGP) was performed via ROP of ε-caprolactone, whereas PPGP act as a multisite macroinitiator. The prepared poly(propylene glycol phosphazene)-graft-polycaprolactone (PPGP-g-PCL) were evaluated by essential tests, including NMR, FTIR, FESEM-EDS, TGA, DSC and contact angle measurement. The quantum calculations were performed to investigate molecular geometry and its energy, and HOMO and LUMO of PPGP-g-PCL in Materials Studio2017. MD simulations were applied to describe the interaction of the polymer on phospholipid membrane (POPC128b) in Material Studio2017. The C2C12 and L929 cells were used to probe the cell-surface interactions on synthetic polymers surfaces. Cells adhesion and proliferation onto scaffolds were evaluated using FESEM and MTT assay. In vitro analysis indicated enhanced cell adhesion, high proliferation rate, and excellent viability on scaffolds for both cell types. The polymer was further tested via intraperitoneal implantation in mice that showed no evidence of adverse inflammation and necrosis at the site of the scaffold implantation; in return, osteogenesis, new-formed bone and in vivo degradation of the scaffold were observed. Herein, in vitro and in vivo assessments confirm PPGP-g-PCL, as an appropriate scaffold for tissue engineering applications., (© 2022. The Author(s).)

Cobalt(III) complexes with Schiff base ligands derived from hydrazone, ( HL 1  = ( E )- N '-(3,5-dichloro-2-hydroxybenzylidene)-4-hydroxybenzohydrazide, HL 2  = ( E )- N '-(3,5-dichloro-2-hydroxybenzylidene)-4-hydroxybenzohydrazide (3,5-dibromo-2-hydroxybenzylidene), and HL 3  = ( E )-4-hydroxy- N '-(2-hydroxy-3-ethoxybenzylidene)benzohydrazide), were synthesized and characterized by elemental analysis, Fourier transform infrared (FT-IR) spectroscopy, UV-Vis spectroscopy, and cyclic voltammetry. X-ray diffraction was used to determine the single crystal structure of the complex ( 1 ). Co(III) was formed in a distorted, very regular octahedral coordination in this complex; three pyridine moieties complete this geometry. Schiff base complexes' redox behaviors are represented by irreversible ( 1 ), quasi-reversible ( 2 ), and quasi-reversible ( 3 ) voltammograms. A density functional theory (DFT)/B3LYP method was used to optimize cobalt complexes with a base set of 6-311G. Furthermore, fragments occupying the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were investigated at the same theoretical level. Quantum theory of atoms in molecules (QTAIM) computations were also done to study the coordination bonds and non-covalent interactions in the investigated structures. Hirshfeld surface analysis was used to investigate the nature and types of intermolecular exchanges in the crystal structure of the complex ( 1 ). The capacity of cobalt complexes to bind to the major protease SARS-CoV-2 and the molecular targets of human angiotensin-converting enzyme-2 (ACE-2) was investigated using molecular docking. The molecular simulation methods used to assess the probable binding states of cobalt complexes revealed that all three complexes were stabilized in the active envelope of the enzyme by making distinct interactions with critical amino acid residues. Interestingly, compound ( 2 ) performed better with both molecular targets and the total energy of the system than the other complexes., (© 2022 John Wiley & Sons Ltd.)

In this study, four novel phosphoramide ligands (L1-L4) are synthesized and characterized by 31 PNMR, 1 HNMR, MASS, and FT-IR spectroscopies. In vitro cell growth inhibition is studied by the MTT assay to evaluate the cytotoxicity of ligands against MCF-7 cell line; the result of the assay demonstrates that all ligands significantly suppress the proliferation of breast cancer cells in a concentration-dependent manner. The calculated IC 50 values are in the range of 3.6-10.77 µg ml -1 , of which the lowest value is attributed to L1. Then a facile approach was developed to functionalize graphene oxide (GO) surface by L1. The data which are obtained by XRD, FT-IR, and EDX analysis confirmed the deposition of phosphoramide on the surface of GO. The cell viability of GO-L1 compound at different concentrations is investigated in 24 h experiment. Excellent synergistic antitumor effects of GO and L1 lead to a decrease in IC 50 value up to 2.13 μg ml -1 . The Quantum calculations of compounds are used to study energies and HOMO and LUMO values, dipole moments (µ), global hardness (η), global softness (σ), and electrophilicity index (ω) using DMol 3 module in Material studio2017. The docking calculations are performed to describe the mode of the binding to DNA and DNA polymerase IIα. Adsorption calculations of ligands (L1-L4) on GO sheet in the presence of water showed that L1 and L2 were located on GO via π electrons of anisole ring. While, L3 and L4 were located on GO by π - π interactions of aniline ring., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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-Fe 3 O 4 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 Fe 3 O 4 @SiO 2 @APTS ∼ Schiff base-Cu(II) (IC 50 : 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.