Search Results (4)

Autophagy is the multistep mechanism for the elimination of damaged organelles and misfolded proteins. This mechanism is preceded and may induce other program cell deaths such as apoptosis. This study unraveled the potential pharmacological effect of 24MD in inducing the autophagy of lung cancer cells. Results showed that 24MD was concomitant with autophagy induction, indicating by autophagosome staining and the induction of ATG5, ATG7 and ubiquitinated protein, p62 expression after 12-h treatment. LC3-I was strongly conversed to LC3-II, and p62 was downregulated after 24-h treatment. The apoptosis-inducing activity was found after 48-h treatment as indicated by annexin V-FITC/propidium iodide staining and the activation of caspase-3. From a mechanistic perspective, 24-h treatment of 24MD at 60 μM substantially downregulated p-mTOR. Meanwhile, p-PI3K and p-Akt were also suppressed by 24MD at concentrations of 80 and 100 μM, respectively. We further confirmed m-TOR-mediated autophagic activity by comparing the effect of 24MD with rapamycin, a potent standard mTOR1 inhibitor through Western blot and immunofluorescence assays. Although 24MD could not suppress p-mTOR as much as rapamycin, the combination of rapamycin and 24MD could increase the mTOR suppressive activity and LC3 activation. Changing the substituent groups (R groups) from dimethylphenol to ethylphenol in EMD or changing methylazanedyl to cyclohexylazanedyl in 24CD could only induce apoptosis activity but not autophagic inducing activity. We identified 24MD as a novel compound targeting autophagic cell death by affecting mTOR-mediated autophagy. Full article

Among lanthanide-based compounds, cerium compounds exhibit a significant role in a variety of research fields due to their distinct tetravalency, high economic feasibility, and high stability of Ce(IV) complexes. Herein, a systematic investigation of crystallographic information, chemical properties, and mechanistic formation of the novel Ce(IV) complex synthesized from cerium(III) nitrate hexahydrate and 2,2′-(methylazanediyl)bis(methylene)bis(4-methylphenol) (MMD) ligand has been explored. According to the analysis of the crystallographic information, the obtained complex crystal consists of the Ce(IV) center coordinated with two nitrate ligands and two bidentate coordinated (N-protonated and O,O-deprotonated) MMD ligands. The fingerprint plots and the Hirshfeld surface analyses suggest that the C–H⋯O and C–H⋯π interactions significantly contribute to the crystal packing. The C–H⋯O and C–H⋯π contacts link the molecules into infinite molecular chains propagating along the [100] and [010] directions. Synchrotron powder X-ray diffraction (XRD) and X-ray absorption spectroscopy (XAS) techniques have been employed to gain an understanding of the oxidative complexation of Ce(IV)-MMD complex in detail. This finding would provide the possibility to systematically control the synthetic parameters and wisely design the precursor components in order to achieve the desired properties of novel materials for specific applications. Full article

Dihydro-1,3,2H-benzoxazine dimer derivatives or dihydro-benzoxazine dimers are a class of compounds typically prepared by ring-opening reactions between dihydro-benzoxazines and phenols. Dihydro-benzoxazine dimers act as chelating agents for several transition and rare-earth cations. To better understand the chelating properties, it is necessary to examine their structural features and electrochemical characteristics thoroughly. However, the electrochemical properties of dihydro-benzoxazine dimers have not been tremendously examined. Herein, eight derivatives of dihydro-benzoxazine dimers possessing different substituents on the benzene ring and the tertiary-amine nitrogen were synthesized as model compounds to investigate their influences on crystal structures and electrochemical properties. The crystal structure of the dihydro-benzoxazine dimer, namely 2,2′-(cyclohexylazanediyl)bis(methylene)bis(4-methoxyphenol) (7), is identified for the first time and further used to compare with the crystal structures of other derivatives reported previously. For all the derivatives, intermolecular O–H⋅⋅⋅O hydrogen bonds are the significant interactions to hold the crystal packing of (7) and also the other derivatives. Hirshfeld surface analyses confirm the presence of intermolecular O–H⋅⋅⋅O hydrogen bonds. Redox behavior of the eight dihydro-benzoxazine dimers was studied by cyclic voltammetry. An oxidation peak observed at 0.25–0.47 V corresponds to the oxidation of the phenolic –OH group to the phenoxonium intermediate. The shift in the electrochemical peak positions is due to the different abilities of the substituents to stabilize the phenoxonium cation intermediate. The stabilizing power is ranged in the following order: methoxy > dimethyl > ethyl ≈ methyl, and N-cyclohexyl > N-methyl. Thus, the derivative (7), which contains both the methoxy and N-cyclohexyl groups, has the lowest oxidation potential. Our work elucidates the effect of the substituents on the crystal structures and electrochemical properties of the dihydro-benzoxazine dimers. Full article

N,N-bis(2-hydroxybenzyl)alkylamines, benzoxazine dimers, are the major product produced from benzoxazine monomers on mono-functional phenol by the one step ring opening reaction. Due to the metal responsive property of benzoxazine dimers, in this present work, N,N-bis(5-methyl-2-hydroxybenzyl)methylamine (MMD), N,N-bis (5-ethyl-2-hydroxybenzyl)methylamine (EMD), and N,N-bis(5-methoxy-2-hydroxybenzyl) methyl amine (MeMD), are considered as novel ligands for rare earth metal ion, such as cerium(III) ion. The complex formed when the clear and colorless solutions of cerium nitrate and benzoxazine dimers were mixed, results in a brown colored solution. The metal-ligand ratios determined by the molar ratio and the Job’s methods were found to be in a ratio of 1:6. To clarify the evidence of the complex formation mechanism, the interactions among protons in benzoxazine dimers both prior to and after the formation of complexes were determined by means of ¹H-NMR, 2D-NMR and a computational simulation. The single phase ceria (CeO₂) was successfully prepared by thermal decomposition of the Ce(III)-benzoxazine dimer complexes at 600 °C for 2 h, was then characterized using XRD. In addition, the ceria powder investigated by TEM is spherical with an average diameter of 20 nm. Full article