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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. [ABSTRACT FROM AUTHOR]

Graphene oxide (GO) nanocomposites have attracted much attention in biomedical and catalytic fields due to their outstanding water dispersibility, cell permeability, high mobility of charge carriers, etc. This article reports the successful synthesis of GO–Co3O4 and phytic acid (PA)-modified GO–Co3O4 (GO–Co3O4–PA) nanocomposites by a facile hydrothermal method and studies of their antiproliferative properties. Various analyses were performed to characterize the synthesized nanocomposites. XRD revealed the characteristic crystallinity of GO–Co3O4 and GO–Co3O4–PA. FT-IR spectroscopy identified the different functional groups of nanocomposites. FE-SEM, AFM, EDX, and DLS analyses of GO–Co3O4–PA demonstrated multigonal particles with an average size of 837 nm on the basal planes of GO with signatures of Co and P. The zeta potential was −49.9 mV for GO–Co3O4–PA, which showed the moderate stability of nanocomposites. The Raman spectra of GO–Co3O4 and GO–Co3O4–PA nanocomposites indicated an increase in the surface defect density of GO due to the adsorption of Co3O4 and PA on the surface of GO. The use of nanocomposites for targeted breast cancer therapy was evaluated via an MTT assay. GO–Co3O4–PA showed considerable cytotoxicity with an IC50 value of 12.94 μg mL−1 towards the breast cancer cell line (MCF-7), which was five times lower than that of GO–Co3O4 (64.36 μg mL−1). As an anticancer agent, PA enhances the interaction of MCF-7 cell lines with nanocomposites and leads to higher cytotoxicity. MTT cytotoxicity, Annexin V/PI double staining, and intracellular reactive oxygen species (ROS) assays were performed. The GO–Co3O4–PA nanocomposite is a promising candidate for breast cancer therapy. Quantum mechanical calculations based on the DFT-D correction and PA adsorption on GO and GO–Co3O4 (1 0 0) in the presence of water were done in the adsorption locator module. Free energy calculations showed that adsorption is a spontaneous and more favorable process. Molecular docking studies were conducted to investigate the interaction of compounds on human topoisomerase IIα bound to DNA (4fm9) and Bcl-2 protein. The results indicated that GO–Co3O4–PA could properly dock into more amino acids with high negative energy scores and confirmed the MTT data. Moreover, GO–Co3O4–PA nanocomposites exhibited excellent catalytic ability towards the Biginelli reaction and showed significant advantages including excellent yields, mild reaction conditions, and short reaction times. [ABSTRACT FROM AUTHOR]

In the current study, we introduced a new water‐soluble polyphosphazene containing hydroxyl groups, poly(propyleneglycol)phosphazene (PPGP). The PPGP is converted to PPGP‐TiO2 cross‐linked polymer via hydrothermal reaction with Ti(OBu)4. The properties of the obtained polymers were assessed by 1H‐NMR, 31P‐NMR, Fourier transform infrared spectroscopy (FTIR) and X‐ray diffraction (XRD) spectroscopic methods, thermal techniques (DSC‐TGA), FESEM–EDX investigations, cyclic voltammetry (CV) and Zeta potential measurements. In order to predict PPGP‐TiO2 cross‐linked polymer structure and obtain HOMO–LUMO maps and COMSO sigma profile, quantum calculations were used by DMol3 module based on Dispersion‐corrected density functional theory (DFT‐D) in Materials Studio Software2017. As a common bone substitute material, hydroxyapatite (HAp) was prepared using a modified method and closely characterized by appropriate analysis. The PPGP cytotoxicity was examined using C2C12 and L929 cell lines and Escherichia coli. The C2C12 differentiation using PPGP (as media supplement) was quantified by alkaline phosphatase activity assay. The biocompatibility of PPGP‐TiO2 was compared with HAp using mentioned cell lines and acute inflammatory testing. The results demonstrated that cell proliferation and osteoblastic differentiation increased in presence of PPGP. Both in vitro and in vivo evidence indicated that the novel scaffold had significant viability, exhibiting notable adaptability with its surrounding living tissue. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The present study was conducted to design and develop new complexes and their metal-based nanodrug (registered as Casiopeínas® for cancer) with a low toxicity, high efficiency, and high selectivity. First, complexes ([Cu(TTA)(bpy)2] (1) and [Cu(TTA)2(en)] (2) (TTA = 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione) were synthesized and characterized by X-ray diffraction studies, CHN analysis, conductivity measurements, FT-IR and UV-vis spectroscopy. Second, nanoparticles (NPs) of 3 and 4 with the average size of 63.04 and 85.39 nm were prepared with ultrasound. Scanning electron microscopy patterns of 3 and 4 showed irregular spherical and nanorod particles with spongy surface. Furthermore, the anticancer properties of compounds and nano-compounds were studied in MKN-45 cell line. Then, apoptosis studies were carried out utilizing AO/EB staining methods. Finally, to confirm the in vitro experimental data, the theoretical study was carried out by molecular docking studies. The results of DNA docking analysis revealed that 1 and 2 were inserted with DNA via the minor groove. The binding affinity monitors the order of 1 > 2, with a preference of binding to A-T over G-C base pairs sequences. [ABSTRACT FROM AUTHOR]

Four new mononuclear copper(II) complexes with methyl acetoacetate and benzoylacetone in the presence of 1,10-phenanthroline and 2,2′-bipyridine were synthesized and characterized by elemental analyses, FT-IR, and UV-Vis spectroscopy. The molecular structures of complexes [Cu(MAA)(bpy)(ClO4)] (1a), [Cu(bzac)(bpy)]ClO4 (2a), [Cu(MAA)(phen)(ClO4)] (1b) and [Cu(bzac)(phen)(ClO4)] (2b) were determined by single crystal X-ray diffraction technique. 1a, 1b, and 2b are five coordinate with a distorted square pyramidal geometry and the structure of 2a consists of isolated [Cu(bzac)(bpy)]+ cations and perchlorate counter anions. The electrochemical studies of copper complexes in acetonitrile solution showed that CuII/CuI reduction processes are electrochemically irreversible. Cytotoxic activity of complexes was screened, including an MTT assay against gastric cancer cell line (MKN-45). The four Cu(II) complexes exhibited lethal effects against MKN-45 cell lines and the half maximal inhibitory concentration (IC50) values obtained were much lower in comparison with 5-fluorouracil. In addition, MTT and migration studies revealed that benzoylacetone complexes are more active than complexes of methyl acetoacetate against the MKN-45 cancer cell lines. Docking simulations of Cu(II) complexes on DNA revealed that the most stable adducts with DNA bind in the minor groove. All complexes display a binding specificity to the A/T rich regions. [ABSTRACT FROM AUTHOR]

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 Fe 3 O 4 /SiO 2 /APTS(~NH 2 ) 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 Fe 3 O 4 /SiO 2 /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 Fe 3 O 4 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., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Eshaghi Malekshah et al.)