A β-Secretase (BACE1)-inhibiting C-Methylrotenoid Induced by Yeast Elicitation in Abronia nana Suspension Cultures

Suspension cultures of Abronia nana were established to produce C-methylisoflavones. Treatment of the A. nana cultures with yeast elicitor induced boeravinone E (1), with maximum induction at 24 h after elicitor treatment. Of the biotic and abiotic elicitors tested, yeast extract gave the strongest induction of 1. The IC₅₀ value of 1 against β-secretase (β-amyloid cleaving enzyme-1) was 5.57 μM. Other proteases such as trypsin, chymotrypsin, and elastase were not inhibited by concentrations up to 1.0 mM, indicating that inhibition of β-secretase was specific. 1 was noncompetitive in Dixon plot, and Ki value was 3.79 μM.     

A New Bromophenol from the Brown Alga Leathesia nana

A novel bromophenol was isolated from ethanolic extract of the brown alga Leathesia nana S.et G. The structure was elucidated as (E)-3-(2,3-dibromo-4,5-dihydroxyphenyl)-2-methylpropenal by spectroscopic methods including IR, HREIMS, 1D and 2D NMR techniques.     

One-pot synthesis of trans-β-lactams from ferrocenylketene generated by thermal Wolff rearrangement

A series of β-lactams containing the ferrocene moiety were synthesized through the Staudinger reaction between ferrocenylketene generated by the thermal Wolff rearrangement of the corresponding diazo ketone and various imines. The stereochemical outcome has been investigated and the trans-products were isolated as the main products, opposite to the reported results by Bonini and coworkers. The absolute configuration of (±)-trans-1,4-diphenyl-3-ferrocenylazetidin-2-one (3c) was determined by X-ray analysis. The stereoselectivity is discussed from the viewpoint of the reaction mechanism.     

Renin inhibition by substituted piperidines: a novel paradigm for the inhibition of monomeric aspartic proteinases?

BACKGROUND: The aspartic proteinase renin catalyses the first and rate-limiting step in the conversion of angiotensinogen to the hormone angiotensin II, and therefore plays an important physiological role in the regulation of blood pressure. Numerous potent peptidomimetic inhibitors of this important drug target have been developed, but none of these compounds have progressed past clinical phase II trials. Limited oral bioavailability or excessive production costs have prevented these inhibitors from becoming new antihypertensive drugs. We were interested in developing new nonpeptidomimetic renin inhibitors. RESULTS: High-throughput screening of the Roche compound library identified a simple 3, 4-disubstituted piperidine lead compound. We determined the crystal structures of recombinant human renin complexed with two representatives of this new class. Binding of these substituted piperidine derivatives is accompanied by major induced-fit adaptations around the enzyme's active site. CONCLUSIONS: The efficient optimisation of the piperidine inhibitors was facilitated by structural analysis of the renin active site in two renin-inhibitor complexes (some of the piperidine derivatives have picomolar affinities for renin). These structural changes provide the basis for a novel paradigm for inhibition of monomeric aspartic proteinases.     

Analysis of 17β-Estadiol from Sewage in Coastal Marine by Surface Plasmon Resonance Technique

In this study, surface plasmon resonance （SPR） for monitoring 17β-eatradiol （E2） was developed. The small molecule E2 was immobilized on a CM5 sensor chip for an indirect competitive immunoassay to detect E2. The SPR response bahed on the antigen-antibody reaction was measured by injecting the sample solution into the flow system. The limitation of detection was 0.445 μg/L. The developed SPE-SPR system was applied to analyze the seawater samples. Recovery of E2 was 91.6%-93. 1%. Relative standard deviations（RSD） for the E2 assay were between 10.9%-15.1% （n = 3）. The range of determination of E2 samples from the sewage in the coastal marine environ-ment was between ND（lower than detection limit） and ca. 11.78 ng/L.     

Microextraction of 17-β-Estradiol from Medicinal Preparations for the Subsequent Determination by HPLC-UV

Journal of Analytical Chemistry - A method is proposed for the chromatographic determination of 17-β-estradiol in medicinal preparations with the microextraction of the analyte from a sample...     

β-Rhamnosides from 6-thio mannosides

Upon condensation of 6-thio-6-deoxy-mannosyl donors 1,2-cis products are obtained with a high degree of stereoselectivity. Subsequent reductive removal of the 6-thio functionality gives 1,2-cis rhamnosides. The 1,2-cis-selectivity can be rationalized with a product forming (3)H(4)-oxocarbenium, which is in equilibrium with a bridged sulfonium intermediate.     

β-Peptide coatings by surface-initiated polymerization

Homopolymers of β-lactams can be grown by surface-initiated polymerization. These surface-linked β-peptides are living polymers with the potential to be utilized as tunable, protease-resistant interfaces in multiphase structural composites where the characteristics of the interface influence bulk properties.     

Analysis of 17β-Estadiol from Sewage in Coastal Marine Environment by Surface Plasmon Resonance Technique

In this study,surface plasmon resonance(SPR)for monitoring 17β-eatradiol(E2)was developed.The small molecule E2 was immobilized on a CM5 sensor chip for an indirect competitive immunoassay to detect E2.The SPR response based on the antigen-antibody reaction was measured by injecting the sample solution into the flow system.The limitation of detection was 0.445 μg/L.The developed SPE-SPR system was applied to analyze the seawater samples.Recovery of E2 was 91.6%-93.1%.Relative standard deviations(RSD)for the E2 assay were between 10.9%-15.1%(n=3).The range of determination of E2 samples from the sewage in the coastal marine environment was between ND(lower than detection limit)and ca.11.78 ng/L.     

β-Eucryptite by a Sol-Gel Route

-Eucryptite solid solution (LAS) Li2O : Al 2O3 : 3SiO2(113) was prepared via a sol-gel route. Complex solutions of lithium or aluminum salts in ethanol/water mixtures were catalysed by inorganic acids (catalyst/alkoxide ratio 0.1). Different ratios of H2SO4 catalyst were also used.TGA showed that the maximum % yield of LAS 113 occurred using H2SO4 catalyst. Above 400°C exothermic peaks occurred in DSC followed by the glass transition. XRD and IR showed a high crystallinity of -eucryptite solid solution using all acids at the 0.1 ratio with the highest crystallinity for the 0.05 H2SO4 ratio. SEM revealed similar grain sizes in spite of higher acid concentrations. XRD data indicated a change to a tetragonal modification with higher catalyst ratio.     

CXCR4 inhibition suppresses Cd-induced renal oxidative stress,apoptosis, and fibrosis by inhibiting the TGF-β1/Smad pathway

This study aimed to investigate the role and mechanism of CXC chemokine receptor 4 (CXCR4) in cadmium (Cd)-induced renal injury. CXCR4 and TGF-β1/Smad pathway protein levels were detected by western blotting. Indicators related to renal function and oxidative stress factors were assessed and reactive oxygen species (ROS) level was evaluated by staining. TUNEL was used to measure apoptosis rate. PAS and Masson's trichrome staining were used to detect the level of renal fibrosis. The expression of Bcl-2, Bax, Cleaved-caspase 3, fibronectin, and collagen I proteins were detected by western blotting, immunohistochemistry, or immunofluorescence. The expression of CXCR4 was increased in a Cd-induced chronic renal injury model in rats. Si-CXCR4 decreased levels of TGF-β1, TGF-βR1, p-Smad2/Smad2, p-Smad3/Smad3, the renal weight index, urine protein, blood urea nitrogen, blood creatinine, and levels of MDA but raised the levels of SOD and GSH-Px. In addition, si-CXCR4 inhibited apoptosis in Cd-treated rats. CXCR4 inhibition alleviated fibrosis levels in Cd-treated rats. In Cd-treated cells, TGF-β attenuated the suppressive effect of CXCR4 inhibition on the TGF-β1/Smad pathway. TGF-β intervention increased MDA and ROS, and downregulated SOD and GSH-Px. TGF-β attenuated the inhibitory effect of CXCR4 on apoptosis and fibrosis. CXCR4 inhibition decreased levels of Cd-induced renal oxidative stress, apoptosis, and fibrosis by inhibiting the TGF-β1/Smad pathway.     

Chiral spiro-β-lactams from 6-diazopenicillanates

Chiral spiro-β-lactam derivatives have been prepared via stereoselective 1,3-dipolar cycloaddition of 6-diazopenicillanates. Using dipolarophiles such as acrylonitrile, acrylates or methyl vinyl ketone spiro-2-pyrazoline-β-lactams were obtained, whereas the cycloaddition with N-substituted-maleimides afforded spiro-1-pyrazoline-β-lactams. 6-Diazopenicillanates also reacted with electron-deficient alkynes to give the corresponding spiro-3H-pyrazole-β-lactam as single product. The observed stereoselectivity can be explained considering that the major product results from the addition to the less sterically hindered α-side of the β-lactam. Microwave-induced denitrogenation of spiro-1-pyrazoline-β-lactams allowed the stereoselective synthesis of novel spirocyclopropyl-β-lactams. The rationalization of the observed selectivity was supported by electronic structure calculations.     

Synthesis of polyrotaxanes from acetyl-β-cyclodextrin

Polyrotaxanes are intermediary products in the synthesis of topological gels. They are created by inclusion complex formation of hydrophobic linear macromolecules with cyclodextrins or their derivatives. Then, pairs of cyclodextrin molecules with covalently linkage were practically forming the nodes of the semi-flexible polymer network. Such gels are called topological gels and they can absorb huge quantities of water due to the net flexibility allowing the poly(ethylene oxide) chains to slide through the cyclodextrin cavities, without being pulled out altogether. For polyrotaxane formation poly(ethylene oxide) was used like linear macromolecules. There are hydroxyl groups at poly(ethylene oxide) chains, whereby the linking of the voluminous molecules should be made. To avoid the reaction of cyclodextrin OH groups with stoppers, they should be protected by, e.g., acetylation. In this work, the acetylation of the OH groups of β-cyclodextrin was performed by acetic acid anhydride with iodine as the catalyst. The acetylation reaction was assessed by the FTIR and HPLC method. By the HPLC analysis was found that the acetylation was completed in 20 minutes. Inserting of poly(ethylene oxide) with 4000 g/mol molecule mass into acetyl-β-cyclodextrin with 2:1 poly(ethylene oxide) monomer unit to acetyl-β-cyclodextrin ratio was also monitored by FTIR, and it was found that the process was completed in 12 h at the temperature of 10°C. If the process is performed at temperatures above 10°C, or for periods longer than 12 hours, the process of uncontrolled hydrolysis of acetate groups was initiated.     

Synthesis of 6β-Halogenodeoxyneopine from Neopine

(-)-Neopine (1), the Δ^8,14 isomer of codeine, occurs as one of the minor constituents in opium from Papaver somniferum L¹. In opium alkaloids of the morphine group the hydroxyl group in position 6 is readily converted with p-toluenesulfonyl chloride or methanesulfonyl chloride into the respective 6α-O-sulfonyl derivatives². The latter in turn form starting materials for the preparation of other derivatives. Thus, with lithium halides, via a S_N2 mechanism³ the 6β-halogen compounds are formed. It is found that, as a result of the allylic system, under slightly changed reaction conditions codeine itself can also yield the 8β-chloro derivative⁴.     

Corrosion inhibition of steel in molar HCl by triphenyltin2–thiophene carboxylate

The effect of triphenyltin2–thiophene carboxylate (TTC) on the corrosion of steel in hydrochloric acid medium was studied using gravimetric, electrochemical polarisation and electrochemical impedance spectroscopy (EIS) measurements. The percentage inhibition efficiency was found to increase with increasing concentration of inhibitor to reach 97% at 10^?3 M. Polarisation study shows that TTC is an efficient inhibitor and acts as a mixed-type inhibitor. EIS results indicate the increase of resistance transfer (R_T) and the decrease of double layer capacitance (C_dl) with TTC concentration. Triphenyltin2–thiophene carboxylate molecules lead to the formation of a protective layer on the surface of steel. The inhibitor is adsorbed on the steel surface according to Langmuir isotherm.     

Formation of Oligosaccharide from Monosaccharide by Pentacoordinate Oxyphosphorane

PhosphorusphalymanybioChemicalreactions['j,suchasthereactionsofADPandAtw].H....ersofarlndeisknownaboathowthePhoSPhruspeesPartintheformationofoligosaccharides.Duhatheinvesigallonofthereaedonofglucose(l)wAnOxyPhosPhorane(2),weisolatedtheproduCtwhosemolecularweighwasverifiedbytheFAB-MS.ItwasAnownthatwhenglycosidesweremixedwAnAnmetalinns,OulytheadductionsofmoleculewAnalkalimetalionsaPPearedinthehighmassregionlcyAforeddinganaPPrOPateaznountofNa+ormp+tothefinalProdCtS,StrOngadduCtinn…     

Aluminum Ion Removal from Monoaluminum Ovotransferrin by Pyrophosphate

Introduction The transferrins are a family of iron-binding proteins which are the requirement of a synergistic anion for the interaction of these proteins with metals.1,2 Although these proteins consist of a single chain of about 700 amino acid resides, they fold into two distinct, homolo-gous lobes connected by a short polypeptide.2-4 Each lobe contains one high-affinity iron-binding site, which is designated as the C-terminal or the N-terminal site, respectively. The ligands for each iron-b…     

Aluminum Lon Removal from Monoaluminum Ovotransferrin by Pyrophosphate

The rates at which aluminum was removed from the N- and C-terminal monoaluminum ovotransferrins by pyrophosphate were evaluated by UV difference spectra in 0.01 mol/L Hepes, pH=7.4 and at 37℃. Pesudo first-order rate constants as a function of pyrophosphate concentration were measured. The results indicate that the pathways of aluminum removal are different. For the N-terminal binding site, aluminum removal follows simple saturation kinetics, while the removal of aluminum from the C-terminal binding site reverts to the combination of saturation and first-order kinetics. The saturation component is consistent with a rate-limiting conformational change in the protein as has been reported. We propose that the first-order kinetics mechanism is attributed to a pre-equilibrium process. The rate constants of saturation kinetics are accelerated from both terminals with the addition of 0.1 mol/L chloride to the monoaluminum ovotransferrin solutions, whereas the rates of the first-order kinetics are decreased for the C-terminal binding site. The effect of chloride ionic strength causes a continuing increase on kobs for the N- and C-terminal binding sites. Moreover, the kinetics behavior of the N-terminal is more easily affected by chloride than that of the C-terminal. In the experiment presumably the N-terminal site is apparently kinetically more labile than the C-terminal site.