Development of a method to screen and isolate potential α‐glucosidase inhibitors from Panax japonicus C.A. Meyer by ultrafiltration,liquid chromatography,and counter‐current chromatography

A new assay based on ultrafiltration, liquid chromatography and mass spectrometry was developed for the rapid screening and identification of the ligands for α‐glucosidase from the extract of Panax japonicus. Six saponins were identified as α‐glucosidase inhibitors. Subsequently, the specific binding ligands, namely, notoginsenoside R₁, ginsenoside Rb₁, chikusetsusaponin V, chikusetsusaponin IV, chikusetsusaponin IVa, and ginsenoside Rd (the purities were 94.18, 95.43, 96.09, 93.26, 94.50, 93.86%, respectively) were separated by counter‐current chromatography using two‐phase solvent systems composed of tert‐butyl methyl ether, acetonitrile, 0.1% aqueous formic acid (3.8:1.0:4.4, v/v/v) and the solvent system composed of methylene chloride, isopropanol, methanol, 0.1% aqueous formic acid (5.8:1.0:6.0:2.2, v/v/v). The results demonstrate that ultrafiltration, liquid chromatography and mass spectrometry combined with high‐speed counter‐current chromatography might provide not only a powerful tool for screening and isolating α‐glucosidase inhibitors in complex samples but also a useful platform for discovering bioactive compounds for the prevention and treatment of diabetes mellitus.     

Screening anti‐tumor compounds from Ligusticum wallichii using cell membrane chromatography combined with high‐performance liquid chromatography and mass spectrometry

Tyrosine 367 Cysteine‐fibroblast growth factor receptor 4 cell membrane chromatography combined with high‐performance liquid chromatography and mass spectrometry was developed. Tyrosine 367 Cysteine‐HEK293 cells were used as the cell membrane stationary phase. The specificity and reproducibility of the cell membrane chromatography was evaluated using 1‐tert‐butyl‐3‐{2‐[4‐(diethylamino)butylamino]‐6‐(3,5‐dimethoxyphenyl)pyrido[2,3‐d]pyrimidin‐7‐yl}urea, nimodipine and dexamethasone acetate. Then, anti‐tumor components acting on Tyrosine 367 Cysteine‐fibroblast growth factor receptor 4 were screened and identified from extracts of Ligusticum wallichii. Components from the extract were retained on the cell membrane chromatographic column. The retained fraction was directly eluted into high‐performance liquid chromatography with mass spectrometry system for separation and identification. Finally, Levistolide A was identified as an active component from Ligusticum wallichii extracts. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide‐formazan colorimetric assay revealed that Levistolide A inhibits proliferation of overexpressing the mutated receptor cells with dose‐dependent manner. Phosphorylation of fibroblast growth factor receptor 4 was also decrease under Levistolide A treatment. Flex dock simulation verified that Levistolide A could bind with the tyrosine kinase domain of fibroblast growth factor receptor 4. Therefore, Levistolide A screened by the cell membrane chromatography combined with high‐performance liquid chromatography and mass spectrometry can arrest cell growth. In conclusion, the two‐dimensional high‐performance liquid chromatography method can screen and identify potential anti‐tumor ingredients that specifically act on the tyrosine kinase domain of the mutated fibroblast growth factor receptor 4.     

Preliminary selection of clay minerals for the removal of pharmaceuticals,bisphenol A and triclosan in acidic and neutral aqueous solutions

Pharmaceuticals, personal care products and endocrine disruptors demonstrate huge potential to cause adverse ecological health effects at very low concentration in aquatic environment. There is a need to improve current purification technologies used in sewage and drinking-water treatment plants. This article aims at providing new insights into the recent development of natural and modified clay-based sorbents for the removal of aqueous contaminants such as pharmaceuticals and personal care products. The removal of six widely used pharmaceuticals: ibuprofen, diclofenac, ketoprofen, carbamazepine, as well as endocrine disrupting chemicals – bisphenol A and a bactericidal agent, triclosan – was examined by sorption onto eight adsorbents. Sorption was performed using natural and modified clay minerals – montmorillonite (Mt), vermiculite (VER), bentonite (B), kaolinite (K), commercial acid activated montmorillonites K10 and K30, and two carbonaceous-mineral nanocomposites, MtG5%T, BAlG3%C. This study showed that among the tested natural clays, vermiculite is the most promising sorbent for the removal of pharmaceuticals in purification processes. Among the modified clay minerals, the best results were achieved for carbonaceous bentonite and two acid activated montmorillonites K10 and K30. However, the removal of acidic pharmaceuticals on montomorillonite K10 and carbonaceous bentonite was strongly dependent on the pH value. In the case of vermiculite and acid-modified montmorillonite K30, the sorption of the selected compounds was not significantly affected by pH, which is crucial in wastewater treatment. The sorption constant divided by the specific surface area (K_d/A) is proposed to assess whether the surface area or chemical properties of the materials control the sorption process. K_d/A values were relatively high in the case of vermiculite, so it should be noticed that individual and specific surface properties of vermiculite were of crucial importance for sorption.     

Semiclassical Trajectory Studies of Reactive and Nonreactive Scattering of OH(A 2Σ+) by H2 Based on an Improved Full-Dimensional Ab Initio Diabatic Potential Energy Matrix

We present a new full-dimensional diabatic potential energy matrix (DPEM) for electronically nonadiabatic collisions of OH(A ²Σ⁺) with H₂, and we calculate the probabilities of electronically adiabatic inelastic collisions, nonreactive quenching, and reactive quenching to form H₂O+H. The DPEM was fitted using a many-body expansion with permutationally invariant polynomials in bond-order functions to represent the many-body part. The dynamics calculations were carried out with the fewest-switches with time uncertainty and stochastic decoherence (FSTU/SD) semiclassical trajectory method. We present results both for head-on collisions (impact parameter b equal to zero) and for a full range of impact parameters. The results are compared to experiment and to earlier FSTU/SD and quantum dynamics calculations with a previously published DPEM. The various theoretical results all agree that nonreactive quenching dominates reactive quenching, but there are quantitative differences between the two DPEMs and between the b=0 results and the all-b results, especially for the probability of reactive quenching.     

Utilization of photocatalysts in decarboxylative coupling of carboxylic N-hydroxyphthalimide (NHPI) esters

Recently, the visible-light photoredox decarboxylative couplings of N-(acyloxy)phthalimides (NHPI esters) and its derivatives have become an efficient chemical transformation. Under visible light, the NHPI esters undergo a single-electron transfer (SET) process to afford the corresponding carbon or nitrogen radicals that participate in many chemical transformations. The photoredox decarboxylative couplings have been applied to achieve construction of an array of carbon–carbon and carbon–heteroatom bonds as well as the synthesis of carbocycles and heterocycles. This review categorises photocatalysts, discusses the application and catalysis mechanisms of NHPI esters, and details recent progress in this field.     

In Silico Design and SAR Study of Dibenzyl Trisulfide Analogues for Improved CYP1A1 Inhibition

Dibenzyl trisulfide (DTS) is a natural compound with potential cancer-preventive properties occurring in Petiveria alliacea L., an ethnomedicinal plant native to the Americas. Previous studies revealed its inhibitory activity toward cytochrome P450 (CYP)1 enzymes, key in the activation of environmental pollutants. Accordingly, the aim of this study was to design novel DTS analogues, aimed at improving not only inhibitory activity, but also specificity toward CYP1A1. This was achieved by targeting interactions with CYP1A1 residues of identified importance. Three-dimensional structures for the novel analogues were subjected to molecular docking with several CYP isoforms, before being ranked in terms of binding affinity to CYP1A1. With three hydrogen bond donors, two hydrogen bond acceptors, a molecular mass of 361 Da, and a log P of 3.72, the most promising DTS analogue obeys Lipinski's rule of five. Following synthesis and in vitro validation of its CYP1A1-inhibitory properties, this compound may be useful in future cancer-preventive approaches.     

Design and Synthesis of New Withaferin A Inspired Hedgehog Pathway Inhibitors

Withanolides constitute a well-known family of plant-based alkaloids characterised by widespread biological properties, including the ability of interfering with Hedgehog (Hh) signalling pathway. Following our interest in natural products and in anticancer compounds, we report here the synthesis of a new class of Hh signalling pathway inhibitors, inspired by withaferin A, the first isolated member of withanolides. The decoration of our scaffolds was rationally supported by in silico studies, while functional evaluation revealed promising candidates, confirming once again the importance of natural products as inspiration source for the discovery of novel bioactive compounds. A stereoselective approach, based on Brown chemistry, allowed the obtainment and the functional evaluation of the enantiopure hit compounds.     

金-石墨烯修饰电极电化学检测塑料瓶中双酚A

在离子液体碳糊电极(CILE)表面上采用一步电还原法制备了纳米金(nAu)-石墨烯(GR)复合膜修饰电极(nAu-GR/CILE)。研究了双酚A(BPA)在nAu-GR/CILE上的电化学行为,BPA的电极反应过程为受吸附控制的不可逆过程;采用示差脉冲伏安法研究了BPA氧化峰电流和浓度之间的关系,在0.08~400.0μmol/L范围内,检出限为0.021μmol/L(3σ)。将nAu-GR/CILE用于塑料瓶中BPA的检测,与采用高效液相色谱法(HPLC)进行对比,结果表明两种方法对BPA的检测结果相吻合。     

Hyperterpenoids A and B: Two pairs of unprecedented 6/6/4/6/6 polycyclic cyclobutane meroterpenoids with potent neuroprotective and anti-inflammatory activities from Hypericum beanii

Hyperterpenoid A (1) and B (2), two pairs of enantiomers, with an unprecedented 6/6/4/6/6 polycyclic skeleton, along with one known compoud hypermonone A (3) were isolated from Hypericum beanii. The racemate (±)-1 and (±)-2 were successfully separated into the two optically pure enantiomers (ee ≥ 99%) using a preparative HPLC system. Their absolute configurations were elucidated by extensive spectroscopic analyses and single-crystal X-ray diffraction method. The related plausible biogenetic pathways were presented. Compound 1-3 showed significant neuroprotective activity and potential anti-inflammatory activity. The result that (+)-2 and (-)-2 presented different anti-inflammatory properties, may lead us to new discovery of structure activity relationship between racemates, enantiomers, and diastereomers, as well as further research regarding the binding of drugs to target proteins.     

ANiN(A = Li,Na, Mg,Ca)的结构、热力学、弹性和电子性质的第一性原理研究

三元过渡金属氮化物ANiN (A = Li, Na, Mg, Ca)是潜在的可充放电池的电极材料。物理性质,比如热稳定性、电子能隙以及弹性稳定性等,对于这些材料的电池应用都是非常重要的。本文使用第一原理方法,对比研究了ANiN这些材料的结构、动力学、弹性和电子结构性质。对状态方程和声子谱的计算被用来确定体系的稳定结构。对最稳定结构的弹性常数的计算表明,这些稳定结构都满足 Born-Huang的稳定性判据,意味着它们的弹性稳定性。对体系电子结构的计算表明,LiNiN和CaNiN是半金属（half-metals）,MgNiN是磁性材料,而NaNiN是通常的金属。这些材料的磁学性质都通过Stoner理论进行了解释。最后,电荷密度的计算被用来很好地说明了这些材料中的Ni-N成键的特征,表明成键特点主要是离子性的,但明显地混合了共价性。