New N,N-dimethylcarbamate inhibitors of acetylcholinesterase: design synthesis and biological evaluation

A series of N,N-dimethylcarbamates containing a N,N-dibenzylamino moiety was synthesized and tested to evaluate their ability to inhibit Acetylcholinesterase (AChE). The most active compounds 4 and 8, showed 85 and 69% of inhibition at 50 mM, respectively. Furthermore, some basic SAR rules were outlined: an alkyl linker of six methylene units is the best spacer between the carbamoyl and dibenzylamino moieties; electron-withdrawal substituents on aromatics rings of the dibenzylamino group reduce the inhibitory power. Compound 4 produces a slow onset inhibition of AChE and this is not due to the carbamoylation of the enzyme, as demonstrated by the time-dependent inhibition assay of AChE with compound 4 and by MALDI-TOF MS analysis of trypsinized AChE inhibited by compound 4. Instead, compound 4 could act as a slow-binding inhibitor of AChE, probably because of its high conformational freedom due to the linear alkyl chain

Synthesis and characterisation of a new benzamide-containing nitrobenzoxadiazole as a GSTP1-1 inhibitor endowed with high stability to metabolic hydrolysis

The antitumor agent 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (1) is a potent inhibitor of GSTP1-1, a glutathione S-transferase capable of inhibiting apoptosis by binding to JNK1 and TRAF2. We recently demonstrated that, unlike its parent compound, the benzoyl ester of 1 (compound 3) exhibits negligible reactivity towards GSH, and has a different mode of interaction with GSTP1-1. Unfortunately, 3 is susceptible to rapid metabolic hydrolysis. In an effort to improve the metabolic stability of 3, its ester group has been replaced by an amide, leading to N-(6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexyl)benzamide (4). Unlike 3, compound 4 was stable to human liver microsomal carboxylesterases, but retained the ability to disrupt the interaction between GSTP1-1 and TRAF2 regardless of GSH levels. Moreover, 4 exhibited both a higher stability in the presence of GSH and a greater cytotoxicity towards cultured A375 melanoma cells, in comparison with 1 and its analog 2. These findings suggest that 4 deserves further preclinical testing

Synthesis of 4-thio-5-(2′′-thienyl)uridine and cytotoxicity activity against colon cancer cells <i>in vitro</i>

A novel anti-tumor agent 4-thio-5-(2′′-thienyl)uridine (6) was synthesized and the in vitro cytotoxicity activity against mice colon cancer cells (MC-38) and human colon cancer cells (HT-29) was evaluated by MTT assay. The results showed that the novel compound had antiproliferative activity toward MC-38 and HT-29 cells in a dose-dependent manner. The cell cycle analysis by flow cytometry indicated that compound 6 exerted in tumor cell proliferation inhibition by arresting HT-29 cells in the G2/M phase. In addition, cell death detected by propidium iodide staining showed that compound 6 efficiently induced cell apoptosis in a concentration-dependent manner. Moreover, the sensitivity of human fibroblast cells to compound 6 was far lower than that of tumor cells, suggesting the specific anti-tumor effect of 4-thio-5-(2′′-thienyl)uridine. Taken together, novel compound 6 effectively inhibits colon cancer cell proliferation, and hence would have potential value in clinical application as an antitumor agent

A New Pseudopolymorph of Hexakis-(4-cynaophenyl)benzene

The title compound (systematic name: benzene-4,4′,4′′,4′′′,-4′′′′,4′′′′′-hexaylhexabenzonitrile dichloromethane disolvate), C48H24N6•2CH2Cl2, crystallizes as an inclusion compound during the slow diffusion of methanol into a solution of hexakis(4-cyanophenyl)benzene in CH2Cl2. The hexakis(4- cyanophenyl)benzene molecule lies on an axis of twofold rotation in the space group Pbcn. Weak C—H•••N interactions between hexakis(4-cyanophenyl)benzene molecules define an open network with space for including guests. The resulting structure is a new pseudopolymorph of hexakis-(4-cyanophenyl)benzene. The eight known pseudopolymorphs have few shared architectural features, in part because none of the intermolecular interactions that are present plays a dominant role or forces neighboring molecules to assume particular relative orientations

Novel Magnetic and Thermodynamic Properties of Thiospinel Compound CuCrZrS4_{4}

We have carried out dc magnetic susceptibility, magnetization and specific heat measurements on thiospinel CuCrZrS$_{4}$. Below $T_{\rm C}^{*} =$ 58 K, dc magnetic susceptibility and magnetization data show ferromagnetic behavior with a small spontaneous magnetization 0.27 $\mu_{\rm B}/$f. u.. In dc magnetic susceptibility, large and weak irreversibilities are observed below $T_{\rm f} =$ 6 K and in the range $T_{\rm f}< T < T_{\rm C}^{*}$ respectively. We found that there is no anomaly as a peak or step in the specific heat at $T_{\rm C}^{*}$.Comment: 11 pages, 4 figure

Vibrational analysis of Ag3(PO2NH)3, Na3(PO2NH)3.H2O, Na3(PO2NH)3.4H2O, [C(NH2)3]3(PO2NH)3.H2O and (NH4)4(PO2NH)4.4H2O

FT IR and FT Raman spectra of Ag3(PO2NH), (Compound I), Na3(PO2NH)3.H2O (Compound II), Na3(PO2NH)3.4H2O (Compound III), [C(NH2)3]3(PO2NH)3.H2O (Compound IV) and (NH4)4(PO2NH)4.4H2O (Compound V) are recorded and analyzed on the basis of the anions, cations and water molecules present in each of them. The PO2NH− anion ring in compound I is distorted due to the influence of Ag+ cation. Wide variation in the hydrogen bond lengths in compound III is indicated by the splitting of the v2 and v3 modes of vibration of water molecules. The NH4 ion in compound V occupies lower site symmetry and exhibits hindered rotation in the lattice. The correlations between the symmetric and asymmetric stretching vibrations of P-N-P bridge and the P-N-P bond angle have also been discussed

Superconductivity at 38 K in Iron-Based Compound with Platinum-Arsenide Layers Ca10(Pt4As8)(Fe2-xPtxAs2)5

We report superconductivity in novel iron-based compounds Ca10(PtnAs8)(Fe2-xPtxAs2)5 with n = 3 and 4. Both compounds crystallize in triclinic structures (space group P-1), in which Fe2As2 layers alternate with PtnAs8 spacer layers. Superconductivity with a transition temperature of 38 K is observed in the n = 4 compound with a Pt content of x ~ 0.36 in the Fe2As2 layers. The compound with n = 3 exhibits superconductivity at 13 K.Comment: OPEN SELECT article, 11 pages, 5 figures, 2 table

Semimetal to semimetal charge density wave transition in 1T-TiSe2_2

We report an infrared study on 1$T$-TiSe$_2$, the parent compound of the newly discovered superconductor Cu$_x$TiSe$_2$. Previous studies of this compound have not conclusively resolved whether it is a semimetal or a semiconductor: information that is important in determining the origin of its unconventional CDW transition. Here we present optical spectroscopy results that clearly reveal that the compound is metallic in both the high-temperature normal phase and the low-temperature CDW phase. The carrier scattering rate is dramatically different in the normal and CDW phases and the carrier density is found to change with temperature. We conclude that the observed properties can be explained within the scenario of an Overhauser-type CDW mechanism.Comment: 4 pages, 4 page

Optical study of interactions in a d-electron Kondo lattice with ferromagnetism

We report on a comprehensive optical, transport and thermodynamic study of the Zintl compound Yb$_{14}$MnSb$_{11}$, demonstrating that it is the first ferromagnetic Kondo lattice compound in the underscreened limit. We propose a scenerio whereby the combination of Kondo and Jahn-Teller effects provides a consistent explanation of both transport and optical data.Comment: 4 page