Phosphatase-inhibitory activity and activation of murine macrophages by new 5'-nucleotidase inhibitors, NPF-86IA, NPF-86IB, NPF-86IIA and NPF-86IIB

New 5'-nucleotidase-inhibitory polyphenols named NPF-86IA, NPF-86IB, NPF-86IIA and NPF-86IIB were isolated from the seeds of Areca catechu L. The ability of the inhibitors to precipitate gelatin was investigated by microturbidimetry. These inhibitors produced weak turbidity. As 5'-nucleotidase is a kind of phosphatase, we examined the effects of these inhibitors on alkaline and acidic phosphatases. While they showed moderate inhibitory effects on the activity of acidic phosphatases, they did not have any significant effect on the activity of alkaline phosphatase. Therefore, they showed a higher inhibitory effect on the 5'-nucleotidase than the other phosphatases, Murine macrophages were directly stimulated by the 5'-nucleotidase inhibitors.     

Synthesis,Characterization, and Evaluation of Antibacterial and Antioxidant Activities of Novel Benzoxazinones and Benzoxathiinones

In this work, the new benzoxazinones and benzoxathiinones were synthesized from reaction of alkyl X‐phenylpropiolates and aminophenol (or 2‐mercaptophenol) in the presence of triphenylphosphine. Their antibacterial activities were studied against Gram‐positive bacteria and Gram‐negative bacteria using the disc diffusion method. The obtained results showed that these compounds are more effective against Gram‐positive bacteria than against Gram‐negative bacteria. Also, evaluation of antioxidant activity of the obtained products showed that they have high to excellent antioxidant activity (79.2–93.6%).     

One-pot three-component azide-alkyne cycloaddition: Synthesis of new pyrazole, 1,2,3-triazole,and oxadiazole tethered and their anti-inflammatory,quantitative structure-activity relationship,and docking studies

A simple and efficient one-pot three-component azide-alkyne cycloaddition of 5-chloro-1-phenyl-pyrazole-4-carbaldehyde with 2-(prop-2-yn-1-ylthio)-5-(substituted phenoxy)methyl-1,3,4-oxadiazole and sodium azide is reported. The newly synthesized compounds were characterized by spectral and analytical data. They were screened for in vitro anti-inflammatory activity by bovine serum albumin denaturation assay. All the tested compounds showed moderate anti-inflammatory activity, whereas three compounds ( 4d , 4i , and 4k ) showed excellent activity comparable with that of the standard drug diclofenac sodium. The quantitative structure-activity relationship (QSAR) study was carried out for anti-inflammatory activities of the synthesized compounds and developed a QSAR model. Inspired by their in vitro anti-inflammatory activities, they were docked to the active site of COX-2 to know the anti-inflammatory potency in silico.     

Design, synthesis, and biological evaluation of somatostatin-based radiopeptides

The prototypes for tumor targeting with radiolabeled peptides are derivatives of somatostatin. Usually, they primarily have high affinity for somatostatin receptor subtype 2 (sst2), and they have moderate affinity for sst5. We aimed at developing analogs that recognize different somatostatin receptor subtypes for internal radiotherapy in order to extend the present range of accessible tumors. We synthesized DOTA-octapeptides based on octreotide by replacing Phe3 mainly with unnatural amino acids. The affinity profile was determined by using cell lines transfected with sst1-5. Internalization was determined by using AR42J, HEK-sst3, and HEK-sst5 cell lines, and biodistribution was studied in rat tumor models. Two of the derivatives thus obtained showed an improved binding affinity profile, enhanced internalization into cells expressing sst2 and sst3, respectively, and better tumor:kidney ratios in animals.     

新型光系统II抑制剂的设计、合成和生物活性测定

根据药效团模型,合理设计并合成了新型光系统II(PSII)抑制剂化合物,进行 了元素分析和红外、紫外及核磁数据表征。希尔反应测试表明,亿合成的化合物均 具有抑制光系统II电子传递功能的生物活性,有的化合物活性较高,为新型PSII除 草剂的开发显示了广阔的应用前景。     

Antibacterial effect,efflux pump inhibitory (NorA,TetK and MepA) of Staphylococcus aureus and in silico prediction of α, β and δ-damascone compounds

ObjectiveThe present study aimed to evaluate the antibacterial effect and inhibitory capacity against NorA, TetK and MepA efflux pump of Staphylococcus aureus multiresistant by in vitro and in silico approach of α, β and δ-damascone compounds.ResultsThe compounds α, β and δ-damascone showed a clinically relevant effect against S. aureus ATCC 6538 standard strain. A modulating effect was also observed in association with antibiotics against MDR strains. Regarding the inhibition of the efflux pump, the compounds showed a modulating effect with antibiotics, against SA-1199, SA-1199B, SA IS-58 and K2068. Only δ-damascone demonstrated an efflux pump inhibitory effect. Regarding ADME properties, α, β and δ-damascone showed similar physicochemical properties with good pharmacokinetic characteristics, such as lipophilicity, oral bioavailability and low toxicity. In addition, they exhibited the binding energy and Ligand Efficiency (LE) ?81.17 (5.4), ?77.48(-5.4) and ?64.55 (-5.1), which shows good interactions with the critical residues of the MepA receptor.ConclusionsFrom the results it is concluded that the compounds α, β and δ-damascone do not have antibacterial activity, but show a modulating effect in association with antibiotics, as well as not showing direct activity on the efflux pump, but they do have a modulating effect with antibiotics and with EtBr (α and β-damascone).     

Preparation, characterization, and application of multistimuli-responsive microspheres with fluorescence-labeled magnetic cores and thermoresponsive shells

Novel functional microspheres with multistimuli-responsive properties have been prepared and characterized. The as-prepared microspheres respond to an external magnetic field, environmental temperature, and ultraviolet radiation. The in vitro drug-loading efficiency and drug-release behavior of these microspheres demonstrated that they could be used as drug carriers for drug controlled release. The results of in vivo distribution investigations of these microspheres showed that they exhibit a high magnetic-targeting effect, which holds promise for applications in various fields such as magnetic drug targeting and tissue labeling, among others.     

Monolithic Silica Columns for HPLC,Micro‐HPLC,and CEC

Two types of monolithic silica columns derivatized to form an ODS phase, one prepared in a fused silica capillary (SR‐FS) and the other prepared in a mold and clad with an engineering plastic (poly‐ether‐ether‐ketone) (SR‐PEEK), were evaluated. The column efficiency and pressure drop were compared with those of a column packed with 5‐μm ODS‐silica particles and of an ODS‐silica monolith prepared in a mold and wrapped with PTFE tubing (SR‐PTFE). SR‐FS gave a lower pressure drop than a column packed with 5‐μm particles by a factor of 20, and a plate height of 20 μm at a linear velocity below 1 mm/s. SR‐PEEK showed higher flow‐resistance than the other monolithic silica columns, but they still showed a minimum plate height of 8–10 μm and a lower pressure drop than popular commercial columns packed with 5‐μm particles. The evaluation of SR‐FS columns in a CEC mode showed much higher efficiency than in a pressure‐driven mode.     

Thunberginols C, D, and E, new antiallergic and antimicrobial dihydroisocoumarins, and thunberginol G 3'-O-glucoside and (-)-hydrangenol 4'-O-glucoside, new dihydroisocoumarin glycosides, from Hydrangeae Dulcis Folium.

New antiallergic and antimicrobial dihydroisocoumarins, thunberginols C, D, and E, were isolated from Hydrangeae Dulcis Folium, the fermented and dried leaves of Hydrangea macrophylla SERINGE var. thunbergii MAKINO, together with new dihydroisocoumarin glycosides, thunberginol G 3'-O-glucoside and (-)-hydrangenol 4'-O-glucoside. Their chemical structures have been determined on the basis of chemical and physicochemical evidence. Thunberginols C, D, E, G, and (-)-hydrangenol 4'-O-glucoside showed antiallergic activity in the in vitro bioassay using the Schults-Dale reaction in sensitized guinea pig bronchial muscle, and they also exhibited antimicrobial activity against oral bacteria.     

Synthesis,characterization, duplex-DNA interactions,and anticancer activities of novel octahedral [Ni(phen)2(dppz-idzo)]2+ and [Co(phen)2(dppz-idzo)]3+ complexes

Two new octahedral [Ni(phen)₂(dppz-idzo)]²⁺ and [Co(phen)₂(dppz-idzo)]³⁺ complexes have been synthesized and characterized by CHN analysis, electrospray ionization-MS, nuclear magnetic resonance, and UV–Vis spectra. The DNA-binding ability of these complexes was spectrophotometrically, hydrodynamically, and electrophoretically evaluated which indicated that they strongly intercalate into the DNA double helix, and that both induced severe DNA damage in the presence of peroxide. The complexes also showed strong antiproliferative effect against HepG2 and MDA-MB-231 cells. By contrast, they were found to be inactive against the MCF-7 cell line. The ligand itself was found to be inactive against the cells tested.     

Preparation,properties, and application of polypropylene micro/nanofiber membranes

Nanofiber membranes have huge potential applications in many areas due to their unique properties. However, the thermoplastic micro/nanofiber membranes were rarely reported. In this paper, polypropylene (PP) nanofibers were prepared by melt extrusion of immiscible blends of PP, cellulose acetate butyrate (CAB), and subsequent removal of the CAB matrix. The wet‐laid application was used to make PP nanofiber membranes and PP‐g‐MAH/nonwoven micro/nanofiber membrane. The properties of membranes including morphology, apparent density, porosity, contact‐angle, pore size distribution, and water flux were characterized. The results showed that the consequent membranes were provided with optimistic porosity and pore size distribution. Moreover, they were all with high pure water fluxes, which were superior to that of PP microporous membrane. They performed an excellent separation performance of TiO₂ suspension and dyeing wastewater. The work revealed this method could be an efficient one to make thermoplastic polymer micro/nanofiber membranes, and they would have a brilliant potential application for water treatment. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis, crystal structures, and properties of 6,12-diaryl-substituted indeno[1,2-b]fluorenes

Fused polycyclic indeno[1,2-b]fluorene derivatives with aryl substituents at the 6,12-positions have been prepared as a potential antiaromatic 20π electronic system. They showed strong absorptions in the visible region and amphoteric redox properties. The quinoid-type molecular structures were revealed by X-ray crystal-structure analysis, which indicated that the bond lengths of the quinoid unit depend on the aryl substituents. Whereas nucleus-independent chemical shift NICS(1) calculations indicate the antiaromatic nature of the s-indacene core, they have higher stability than substituted acene derivatives. The derivatives with difluorophenyl or anthryl groups were stable in solution. Vapor-deposited thin films showed ambipolar carrier transportation in the field-effect transistor devices.     

METHACRYLOYL DERIVITIZED HYPERBRANCHED POLYESTER. 1. SYNTHESIS,CHARACTERIZATION, AND COPOLYMERIZATION

Three hyperbranched multi-methacrylates (H20-MMA, H30-MMA and H40-MMA) have been synthesized by reacting Boltorn dendritic polyols with methacrylic anhydride and methacryloyl chloride. Their structures were characterized by FT-IR and NMR (¹H and ¹³C) and molecular weights were measured by GPC. These multi-methacrylates (H-MMAs) mixed well with a variety of monomers such as acrylic acid (AA), methacrylic acid (MA), methyl methacrylate (MMA), 2-hydroxy-ethyl methacrylate (HEMA), tri(ethylene glycol) dimethdimethacrylate (TEGDMA), and bisphenol A glycidyl dimethacrylate (BisGMA). The initial studies on thermal polymerization activities of 10% of H-MMAs with AA, MA, and MMA showed that they gave higher polymerization enthalpy than the corresponding homopolymerization. The resulting materials showed one glass transition temperature, indicating a typical single-phase resin. The H-MMAs can effectively copolymerize with AA, MA, and MMA, with essentially no homopolymers produced, as indicated by acetone extraction studies. This indicated that the hyperbranched multi-methacrylates have the potential to be used as crosslinking agents or modifiers with a number of monomers to produce new thermosets.     

Two new b-hydroxy amino acid-coupled secoiridoids from the flower buds of Lonicera japonica:Isolation,structure elucidation,semisynthesis,and biological activities

Two new b-hydroxy amino acid-coupled secoiridoids,named serinosecologanin(1) and threoninosecologanin(2),were isolated from an aqueous extract of the flower buds of Lonicera japonica.Their uncommon structures including absolute configurations were determined by spectroscopic data analysis,and confirmed by semisynthesis from the co-occurring secologanin(3) and secologanic acid(4).Compounds 1 and 2 exhibited resistant activity against b-glucosidase from almonds and hesperidinase from Aspergillus niger,they also showed activity against the release of glucuronidase in rat polymorphonuclear leukocytes induced by the platelet-activating factor with inhibition rates of(34.9 3.1)% and(53.6 2.6)%,respectively.     

V2O5/MO-Al2O3（M = Mg，Ca，Sr，Ba）催化剂用于正丁烷催化氧化脱氢反应

采用浸渍法制备了不同V2O5担载量的V2O5/MO-Al2O3(M = Mg, Ca, Sr, Ba)催化剂,钒物种的前驱体为偏钒酸铵.对制备的催化剂进行了一系列表征,并对催化剂上正丁烷选择性氧化脱氢制取丁烯进行了反应研究.表征结果(包括比表面积、X射线衍射、傅里叶红外光谱、氢气程序升温还原和拉曼光谱)显示,不同碱土金属元素掺杂的催化剂显示不同的钒价态信息和催化性能.其中掺杂Ca, Sr, Ba的催化剂,正钒酸盐相很难被还原,因此催化剂的氧化还原循环难以建立,导致以上三种催化剂在正丁烷氧化脱氢反应中活性较低.然而, Mg掺杂的催化剂却显示出较高的催化活性和选择性.实验结果表明：在Mg掺杂的载体上担载5% V2O5的催化剂上600°C时可获得高达30.3%的正丁烷转化率和64.3%的烯烃总选择性.这与V2O5担载量为5%时,在获得高度分散的钒氧化合物物种时可使MgO晶相稳定存在密切相关.     

Synthesis, self-assembly, and charge transporting property of contorted tetrabenzocoronenes

A facile route has been developed for the preparation of a new family of contorted 1.2,3.4,7.8,9.10-tetrabenzocoronenes (TBCs). A two-step cyclization reaction, i.e., oxidative photocyclization followed by FeCl(3)-mediated intramolecular cyclodehydrogenation, was carried out on the olefin precursors to obtain the final TBC compounds. These new TBC molecules have contorted conformation due to steric overcrowding as disclosed by single-crystal crystallographic analysis. Nevertheless, they showed extended π-conjugation compared with coronene and exhibited strong aggregation in solution. The thermal behavior and self-assembly of TBC-C8 in solid were studied by a combination of thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM). Compound TBC-C8 showed very good thermal and photostability and exhibited long-range ordered π-stacking in the bulk state. Moreover, uniform nanofibers with tens of micrometer length are formed in the drop-casted thin films. TBC-C8 also possesses a desirable HOMO energy level (-5.10 eV), which allows efficient charge injection from electrodes such as gold electrode. The charge carrier mobilities were determined by using the space-charge limited-current (SCLC) technique and high average hole mobility of 0.61 cm(2) V(-1) s(-1) was obtained for TBC-C8.     

水杨酰肼Schiff碱的合成、表征及抑菌活性

Sehiff碱具有多个氧、氮配位原子,是一类重要的生物配体,某些Schiff碱具有抗癌、抗病毒、抑制细菌生长等生物活性。本文制备了两个水杨酰肼类Schiff碱化合物,并探讨了结构组成、波谱性能及抑菌活性。     

De novo design, synthesis, and characterization of antimicrobial beta-peptides

beta-Peptides are a class of polyamides that have been demonstrated to adopt a variety of helical conformations. Recently, a series of amphiphilic L(+2) helical beta-peptides were designed, which were intended to mimic the overall physicochemical properties of a class of membrane-active antimicrobial peptides, including magainin and cecropin. Although these peptides showed potent antimicrobial activity, they also showed significant activity against human erythrocytes. Operating under the assumption that their lack of specificity arose from excessive hydrophobicity, two additional beta-peptides H-(beta(3)-HAla-beta(3)-HLys-beta(3)-HVal)(n)-NH(2) (n = 4, 5) were designed and synthesized. Both have high antimicrobial activities, but very low hemolytic potencies. The peptides bind in an L(+2) conformation to phospholipid vesicles, inducing leakage of entrapped small molecules. The peptides have a low affinity for membranes consisting of neutral phosphatidylcholine lipids, but bind avidly to vesicles containing 10 mol % of acidic phosphatidylserine lipids. Differences in vesicle leakage kinetics for the two peptides suggest that chain length could affect their mechanisms of disrupting cell membranes. Thus, insights gained from the study of variants of natural alpha-peptides have provided a useful guide for the design of nonnatural antimicrobial beta-peptides.     

Design,synthesis, and in vitro anticancer screening of novel pyrazolinyl-pyrazole/1, 2, 3-triazole hybrids

Novel hybrids, pyrazolinylpyrazoles, and pyrazolinyltriazoles were designed, synthesized, and screened for their anticancer activity. Eleven compounds were selected by the National Cancer Institute (NCI)/USA for anticancer screening at single high dose (10⁻⁵ M) in full NCI 60 cell panels. Two compounds: 4-aminopyrazole-5-carbonitrile, 5c (NSC-747630/1) and ethyl 4-aminopyrazole-5- carboxylate, 7d (NSC-747634/1) were the most active candidates of the series and were selected for further evaluation at five dose screening as they displayed significant growth inhibition with full panel median growth inhibition (GI₅₀) 5.47 and 2.24 μM, respectively. Both 5c and 7d hybrids exhibited broad spectrum antitumor activity; however 7d showed moderate selectivity (selectivity ratio 3.6) toward leukemia.     

褐藻糖胶的提取纯化及其抗凝血活性的研究

从海带中提取出的水溶性提取物，经超滤，醇析获得褐藻糖胶粗多糖，以DEAE-Sephrose Fast Flow离子交换层析分离纯化，得到了F1，F2和F3三个级分，这三个级分具有明显的抗凝血作用。尤其是F3级分，能显地延长激活部分凝血活酶时间和凝血酶时间。