Predicting hiCE inhibitors based upon pharmacophore models derived from the receptor and its ligands

Human intestinal carboxyl esterase (hiCE) is a drug target for ameliorating irinotecan-induced diarrhea. By reducing irinotecan-induced diarrhea, hiCE inhibitors can improve the anti-cancer efficacy of irinotecan. To find effective hiCE inhibitors, a new virtual screening protocol that combines pharmacophore models derived from the hiCE structure and its ligands has been proposed. The hiCE structure has been constructed through homology techniques using hCES1’s crystal structure. The hiCE structure was optimized via molecular dynamics simulations with the most known active hiCE inhibitors docked into the structure. An optimized pharmacophore, derived from the receptor, was then generated. A ligand-based pharmacophore was also generated from a larger set of known hiCE inhibitors. The final hiCE inhibitor predictions were based upon the virtual screening hits from both ligand-based and receptor-based pharmacophore models. The hit rates from the ligand-based and receptor-based pharmacophore models are 88% and 86%, respectively. The final hit rate is 94%. The two models are highly consistent with one another (85%). This proves that both models are reliable.     

New Cytotoxic Triterpenoids from the Aerial Parts of Euphorbia sieboldiana

Phytochemical investigation of the EtOH extract of Euphorbia sieboldiana led to the isolation of four new oleanane‐type triterpenoids, (1β,2α,3β,19β)‐1,2,3,19‐tetrahydroxyolean‐12‐en‐28‐oic acid, (1β,3β,19β)‐1,3,19‐trihydroxyolean‐12‐en‐28‐oic acid, (1β,2α,3β,16β,19β)‐1,2,3,16,19‐pentahydroxyolean‐12‐en‐28‐oic acid, and (1β,2α,3β,19β,23)‐1,2,3,19,23‐pentahydroxyolean‐12‐en‐28‐oic acid, along with 16 known compounds. Their structures were established by extensive 1D‐ and 2D‐NMR, as well as other spectral analyses. Biological evaluation of the four new triterpenoids revealed potent cytotoxic activities against HeLa and Hep‐G2 cells.     

Enhancement inhibition efficiency of PBTCA depending on the inclusion complex with hydroxypropyl-β-cyclodextrin

For the first time, hydroxypropyl-β-cyclodextrin (HP-β-CD) has been brought in to include 2-phosphonobutane-1,2,4-tricarboxylic acid (PBTCA) in order to enhance inhibition efficiency of PBTCA, which leads a new approach to study oil–gas field corrosion inhibition in the process of acid treatment. Based on the host–guest inclusion reaction, the inclusion complex of PBTCA with HP-β-CD has been prepared in the laboratory. UV–Vis absorption spectrum was applied to study the inclusion behavior of PBTCA with HP-β-CD. The results revealed that PBTCA with HP-β-CD can form a 1:1 stoichiometry inclusion complex. The 1:1 inclusion complex synthesized by using lyophilization was further characterized by Fourier transform infrared spectroscopy. Besides, inhibition effect of the inclusion complex on the corrosion inhibition of Q235 carbon steel has been investigated in 0.1 M sulfuric acid (H₂SO₄) solution using potentiodynamic polarization, electrochemical impedance spectroscopy techniques and scanning electron microscopy (SEM). It was found that the presence of the inclusion complex better achieved the anti-corrosion property in aggressive medium than was the case with alone PBTCA and the highest inhibition efficiency of the inclusion complex over 90 % was obtained, which are suggestive of the active effect of the inclusion complex for improving inhibition efficiency of PBTCA. Meanwhile, the results obtained from SEM further showed that the inclusion complex acts as a more efficient corrosion inhibitor for Q235 carbon steel in H₂SO₄ medium.     

Studies on the Synthesis and Antiproliferative Activities of 13‐cis‐Retinoyl Sugar Derivatives

New retinoyl sugar derivatives of 13‐cis‐retinoic acid were synthesized in three ways in this paper in order to enhance pharmacal effects, especially antiproliferative activities of 13‐cis‐retinoic acid. Their structures were confirmed by IR, ¹H‐NMR, ¹³C‐NMR, and MS spectra and their antiproliferative activities were determined in vitro using human cancer lines. Results showed that some compounds possessed potential antitumor activities.     

Synthesis and application of moisture-stable methallylsilanated phosphorylcholine as a surface modifier

New methallylsilanated phosphorylcholine (MASPCs) were synthesized via a copper-catalyzed ‘click’ reaction and demonstrated excellent moisture stability. Hydroxylated silicon compounds, silanol, and silica were grafted or modified by MASPCs in the presence of triflic acid (TfOH) and they possessed a good grafting efficiency and high loading rate.     

Copper‐Based Ternary and Quaternary Semiconductor Nanoplates: Templated Synthesis,Characterization, and Photoelectrochemical Properties

Two‐dimensional (2D) copper‐based ternary and quaternary semiconductors are promising building blocks for the construction of efficient solution‐processed photovoltaic devices at low cost. However, the facile synthesis of such 2D nanoplates with well‐defined shape and uniform size remains a challenge. Reported herein is a universal template‐mediated method for preparing copper‐based ternary and quaternary chalcogenide nanoplates, that is, CuInS₂, CuIn_xGa_1−xS₂, and Cu₂ZnSnS₄, by using a pre‐synthesized CuS nanoplate as the starting template. The various synthesized nanoplates are monophasic with uniform thickness and lateral size. As a proof of concept, the Cu₂ZnSnS₄ nanoplates were immobilized on a Mo/glass substrate and used as semiconductor photoelectrode, thus showing stable photoelectrochemical response. The method is general and provides future opportunities for fabrication of cost‐effective photovoltaic devices based on 2D semiconductors.     

Determination of glutathione in single HepG2 cells by capillary electrophoresis with reduced graphene oxide modified microelectrode

Determination of intracellular bioactive species will afford beneficial information related to cell metabolism, signal transduction, cell function, and disease treatment. In this study, the electrochemically reduced graphene oxide modified carbon fiber microdisk electrode (ER‐GOME) was used as a detector of CZE‐electrochemical detection and developed to detect glutathione (GSH). The electrocatalytic activity of the modified microelectrode was characterized by cyclic voltammetry. Under optimized experimental conditions, the concentration linear range of GSH was from 1 to 60 μM. When the S/N ratio was 3, the concentration detection limit was 1 μM. Compared with the unmodified carbon fiber microdisk electrode, the sensitivity was enhanced more than five times. With the use of this method, the average contents of GSH in single HepG2 cells were found to be 7.13 ± 1.11 fmol (n = 10). Compared with gold/mercury amalgam microelectrode, which was usually used in determining GSH, the electrochemically reduced graphene oxide modified carbon fiber microdisk electrode was friendly to environment for free mercury. Furthermore, there were several merits of the novel electrochemical detector coupled with CE, such as comparative repeatability, easy fabrication, and high sensitivity, hold great potential for the single‐cell assay.     

Synthesis of 1,4-diarylsubstituted 1,3-diynes through ligand-free copper-catalyzed oxidative decarboxylative homocoupling of aryl propiolic acids

An efficient method of ligand-free Cu-catalyzed oxidative decarboxylative homocoupling of aryl propiolic acids was developed. When CuI was employed as the catalyst and I₂ as the oxidant, the decarboxylative homocoupling reaction for C_sp–C_sp bond formation in DMSO underwent smoothly to afford the corresponding 1,4-disubstituted 1,3-dialkynes in good to excellent yields without any organic ligands. This catalytic system was applicable to aryl propiolic acids bearing different steric, electronic, and functional groups.     

Synthesis,structure and reactivity of a macrocyclic imine: aza-[13]-macrodiolides

The in situ synthesis and subsequent reactions of macrocylic imine 2 are reported. The imine was trapped with cyanotrimethylsilane to give α-amino nitrile aza-[13]-macrodiolides in a 1:1 ratio of diastereomers. A crystal structure of the syn α-cyano nitrile diastereomer, 7a, provided insights into the lack of selectivity in reactions of 2 relative to macrocyclic alkene 1. Reactions to functionalize the syn diastereomer 7a are also reported.