Photoluminescence imaging of europium (III)‐doped γ‐Al2O3 nanofiber structures

Aluminium oxide (Al₂O₃) has widely been used for catalysts, insulators, and composite materials for diverse applications. Herein, we demonstrated if γ‐Al₂O₃ was useful as a luminescence support material for europium (Eu) (III) activator ion. The hydrothermal method and post‐thermal treatment at 800°C were employed to synthesize Eu(III)‐doped γ‐Al₂O₃ nanofibre structures. Luminescence characteristics of Eu(III) ions in Al₂O₃ matrix were fully understood by taking 2D and 3D‐photoluminescence imaging profiles. Various sharp emissions between 580 to 720 nm were assigned to the ⁵D₀→⁷F_J (J = 0, 1, 2, 3, 4) transitions of Eu(III) activators. On the basis of X‐ray diffraction crystallography, Auger elemental mapping and the asymmetry ratio, Eu(III) ions were found to be well doped into the γ‐Al₂O₃ matrix at a low (1 mol%) doping level. A broad emission at 460 nm was substantially increased upon higher (2 mol%) Eu(III) doping due to defect creation. The first 3D photoluminescence imaging profiles highlight detailed understanding of emission characteristics of Eu(III) ions in Al oxide‐based phosphor materials and their potential applications.     

Conformations of peptides containing a chiral cyclic α, α‐disubstituted α‐amino acid within the sequence of Aib residues

A single chiral cyclic α,α‐disubstituted amino acid, (3S,4S)‐1‐amino‐(3,4‐dimethoxy)cyclopentanecarboxylic acid [(S,S)‐Ac₅c^dOM], was placed at the N‐terminal or C‐terminal positions of achiral α‐aminoisobutyric acid (Aib) peptide segments. The IR and ¹H NMR spectra indicated that the dominant conformations of two peptides Cbz‐[(S,S)‐Ac₅c^dOM]‐(Aib)₄‐OEt ( 1) and Cbz‐(Aib)₄‐[(S,S)‐Ac₅c^dOM]‐OMe (2) in solution were helical structures. X‐ray crystallographic analysis of 1 and 2 revealed that a left‐handed (M) 3₁₀‐helical structure was present in 1 and that a right‐handed (P) 3₁₀‐helical structure was present in 2 in their crystalline states. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Polymer‐Supported Optically Active fac(S)‐Tris(thiotato)rhodium(III) Complex for Sulfur‐Bridging Reaction With Precious Metal Ions

The optically active mixed‐ligand fac(S)‐tris(thiolato)rhodium(III) complexes, Δ_L‐fac(S)‐[Rh(aet)₂(L‐cys‐N,S)]^? (aet = 2‐aminoethanethiolate, L‐cys = L‐cysteinate) ( 1 ) and Δ_LL‐fac(S)‐[Rh(aet)(L‐cys‐N,S)₂]^2? were newly prepared by the equatorial preference of the carboxyl group in the coordinated L‐cys ligand. The amide formation reaction of 1 with 1,10‐diaminodecane and polyallylamine gave the diamine‐bridged dinuclear Rh(III) complex and the single‐chain polymer‐supported Rh(III) complex with retention of the Δ_L configuration of 1 , respectively. These Rh(III) complexes reacted with Co(III) or Co(II) to give the linear‐type trinuclear structure with the S‐bridged Co(III) center and the two Δ‐Rh(III) terminal moieties. The polymer‐supported Rh(III) complex was applied not only to the CD spectropolarimetric detection and determination of a trace of precious metal ions such as Au(III), Pt(II), and Pd(II) but also to concentration and extraction of these metal ions into the solid polymer phase. Chirality 28:85–91, 2016. © 2015 Wiley Periodicals, Inc.     

Synthesis and Antiproliferative Activities of Novel Substituted 5‐Anilino‐α‐Glucofuranose Derivatives

In order to find novel antitumor candidate agents with high efficiency and low toxicity, 14 novel substituted 5‐anilino‐α‐glucofuranose derivatives have been designed, synthesized and evaluated for antiproliferative activities in vitro. Their structures were characterized by NMR (¹H and ¹³C) and HR‐MS, and configuration (R/S) at C(5) was identified by two‐dimensional ¹H,¹H‐NOESY‐NMR spectrum. Their antiproliferative activities against human tumor cells were investigated by MTT assay. The results demonstrated that most of the synthesized compounds had antiproliferative effects comparable to the reference drugs gefitinib and lapatinib. In particular, (5R)‐5‐O‐(3‐chloro‐4‐{[5‐(4‐fluorophenyl)thiophen‐2‐yl]methyl}anilino)‐5‐deoxy‐1,2‐O‐(1‐methylethylidene)‐α‐glucofuranose ( 9da ) showed the most potent antiproliferative effects against SW480, A431 and A549 cells, with IC₅₀ values of 8.57, 5.15 and 15.24 μm , respectively. This work suggested 5‐anilino‐α‐glucofuranose as an antitumor core structure that may open a new way to develop more potent anti‐cancer agents.     

Cytotoxic (9βH)‐Pimarane and (9βH)‐17‐Norpimarane Diterpenes from the Tuber of Icacina trichantha

Three (9βH)‐pimaranes, 1, 2 , and 3 , and two (9βH)‐17‐norpimaranes, 4 and 5 , belonging to a rare compound class in nature, were obtained from the tubers of Icacina trichantha for the first time. Compound 1 is a new natural product, and 2 – 5 have been previously reported. The structures were elucidated based on NMR and MS data, and optical rotation values. The absolute configurations of (9βH)‐pimaranes were unambiguously established based on X‐ray crystallographic analysis. Full NMR signal assignments for the known compounds 2, 4 , and 5 , which were not available in previous publications, are also reported. All five isolates displayed cytotoxic activities on MDA‐MB‐435 cells (IC₅₀ 0.66–6.44 μM ), while 2, 3 , and 4 also exhibited cytotoxicities on HT‐29 cells (IC₅₀ 3.00–4.94 μM ).     

Nanostructures from the self‐assembly of α‐helical peptide amphiphiles

Self‐assembly of PAs composed of palmitic acid and several repeated heptad peptide sequences, C₁₅H₃₁CO‐(IEEYTKK)_n‐NH₂ (n = 1–4, represented by PA1–PA4), was investigated systematically. The secondary structures of the PAs were characterized by CD. PA3 and PA4 (n = 3 and 4, respectively) showed an α‐helical structure, whereas PA1 and PA2 (n = 1 and 2, respectively) did not display an α‐helical conformations under the tested conditions. The morphology of the self‐assembled peptides in aqueous medium was studied by transmission electron microscopy. As the number of heptad repeats in the PAs increased, the nanostructure of the self‐assembled peptides changed from nanofibers to nanovesicles. Changes of the secondary structures and the self‐assembly morphologies of PA3 and PA4 in aqueous medium with various cations were also studied. The critical micelle concentrations were determined using a pyrene fluorescence probe. In conclusion, this method may be used to design new peptide nanomaterials. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.     

5α‐Androst‐16‐en‐3α‐ol β‐D‐Glucuronide,Precursor of 5α‐Androst‐16‐en‐3α‐ol in Human Sweat

5α‐Androst‐16‐en‐3α‐ol (α‐androstenol) is an important contributor to human axilla sweat odor. It is assumed that α‐andostenol is excreted from the apocrine glands via a H₂O‐soluble conjugate, and this precursor was formally characterized in this study for the first time in human sweat. The possible H₂O‐soluble precursors, sulfate and glucuronide derivatives, were synthesized as analytical standards, i.e., α‐androstenol, β‐androstenol sulfates, 5α‐androsta‐5,16‐dien‐3β‐ol (β‐androstadienol) sulfate, α‐androstenol β‐glucuronide, α‐androstenol α‐glucuronide, β‐androstadienol β‐glucuronide, and α‐androstenol β‐glucuronide furanose. The occurrence of α‐androstenol β‐glucuronide was established by ultra performance liquid chromatography (UPLC)/MS (heated electrospray ionization (HESI)) in negative‐ion mode in pooled human sweat, containing eccrine and apocrine secretions and collected from 25 female and 24 male underarms. Its concentration was of 79 ng/ml in female secretions and 241 ng/ml in male secretions. The release of α‐androstenol was observed after incubation of the sterile human sweat or α‐androstenol β‐glucuronide with a commercial glucuronidase enzyme, the urine‐isolated bacteria Streptococcus agalactiae, and the skin bacteria Staphylococcus warneri DSM 20316, Staphylococcus haemolyticus DSM 20263, and Propionibacterium acnes ATCC 6919, reported to have β‐glucuronidase activities. We demonstrated that if α‐ and β‐androstenols and androstadienol sulfates were present in human sweat, their concentrations would be too low to be considered as potential precursors of malodors; therefore, the H₂O‐soluble precursor of α‐androstenol in apocrine secretion should be a β‐glucuronide.     

A general method for preparation of N‐Boc‐protected or N‐Fmoc‐protected α,β‐didehydropeptide building blocks and their use in the solid‐phase peptide synthesis

N‐(tert‐butyloxycarbonyl) or N‐(9‐fluorenylmethoxycarbonyl) dipeptides with C‐terminal (Z)‐α,β‐didehydrophenylalanine (?^ZPhe), (Z)‐α,β‐didehydrotyrosine (?^ZTyr), (Z)‐α,β‐didehydrotryptophan (?^ZTrp), (Z)‐α,β‐didehydromethionine (?^ZMet), (Z)‐α,β‐didehydroleucine (?^ZLeu), and (Z/E)‐α,β‐didehydroisoleucine (?^Z/EIle) were synthesised from their saturated analogues via oxidation of intermediate 2,5‐disubstituted‐oxazol‐5‐(4H)‐ones (also known as azlactones) with pyridinium tribromide followed by opening of the produced unsaturated oxazol‐5‐(4H)‐one derivatives in organic‐aqueous solution with a catalytic amount of trifluoroacetic acid or by a basic hydrolysis. In all cases, a very strong preference for Z isomers of α,β‐didehydro‐α‐amino acid residues was observed except of the ΔIle, which was obtained as the equimolar mixture of Z and E isomers. Reasons for the (Z)‐stereoselectivity and the increased stability of the aromatic α,β‐didehydro‐α‐amino acid residue oxazol‐5‐(4H)‐ones over the corresponding aliphatic ones are also discussed. It is the first use of such a procedure to synthesise peptides with the C‐terminal unsaturated residues and a peptide with 2 consecutive ΔPhe residues. This approach is very effective especially in the synthesis of peptides with aliphatic α,β‐didehydro‐α‐amino acid residues that are difficult to obtain by other methods. It allowed the first synthesis of the ?Met residue. It is also more cost‐effective and less laborious than other synthesis protocols. The dipeptide building blocks obtained were used in the solid‐phase synthesis of model peptides on a polystyrene‐based solid support. Peptides containing aromatic α,β‐didehydro‐α‐amino acid residues were obtained with PyBOP or TBTU as a coupling agent with good yields and purities. In the case of aliphatic α,β‐didehydro‐α‐amino acid residues, a good efficiency was achieved only with DPPA as a coupling agent.     

α‐Glucosidase Inhibitors from the Fungus Aspergillus terreus 3.05358

One new diketopiperazine alkaloid amauromine B ( 1 ), along with three known meroterpenoids, austalide B ( 2 ), austalides N and O ( 3 and 4 ), and two known steroids ( 5 and 6 ), was isolated and identified from the culture broth of the fungus Aspergillus terreus 3.05358. Their structures were elucidated by extensive spectroscopic techniques, including 2D‐NMR and MS analysis, the absolute configuration of 1 was unambiguously established by single crystal X‐ray diffraction analysis. All the isolates were evaluated for their inhibitory effects on α‐glucosidase. Amauromine B ( 1 ) and austalide N ( 3 ) exhibited more potent α‐glucosidase inhibitory activities than the positive control acarbose.     

Molecular Insight and Mode of Inhibition of α‐Glucosidase and α‐Amylase by Pahangensin A from Alpinia pahangensis Ridl.

The inhibition of carbohydrate‐hydrolyzing enzymes in human digestive organs is crucial in controlling blood sugar levels, which is important in treating type 2 diabetes. In the current study, pahangensin A ( 1 ), a bis‐labdanic diterpene characterized previously in the rhizomes of Alpinia pahangensis Ridl ., was identified as an active dual inhibitor for α‐amylase (IC₅₀=114.80 μm ) and α‐glucosidase (IC₅₀=153.87 μm ). This is the first report on the dual α‐amylase and α‐glucosidase inhibitory activities of a bis‐labdanic diterpene. The Lineweaver‐Burk plots of compound 1 indicate that it is a mixed‐type inhibitor with regard to both enzymes. Based on molecular docking studies, compound 1 docked in a non‐active site of both enzymes. The dual inhibitory activity of compound 1 makes it a suitable natural alternative in the treatment of type 2 diabetes.     

Enantioselective σ1 receptor binding and biotransformation of the spirocyclic PET tracer 1′‐benzyl‐3‐(3‐fluoropropyl)‐3H‐spiro[[2]benzofuran‐1,4′‐piperidine]

It was shown that racemic (±)‐ 2 [1′‐benzyl‐3‐(3‐fluoropropyl)‐3H‐spiro[[2]benzofuran‐1,4′‐piperidine], WMS‐1813 ] represents a promising positron emission tomography (PET) tracer for the investigation of centrally located σ₁ receptors. To study the pharmacological activity of the enantiomers of 2 , a preparative HPLC separation of (R)‐2 and (S)‐2 was performed. The absolute configuration of the enantiomers was determined by CD‐spectroscopy together with theoretical calculations of the CD‐spectrum of a model compound. In receptor binding studies with the radioligand [³H]‐(+)‐pentazocine, (S)‐2 was thrice more potent than its (R)‐configured enantiomer (R)‐2 . The metabolic degradation of the more potent (S)‐enantiomer was considerably slower than the metabolism of (R)‐2 . The structures of the main metabolites of both enantiomers were elucidated by determination of the exact mass using an Orbitrap‐LC‐MS system. These experiments showed a stereoselective biotransformation of the enantiomers of 2 . Chirality, 2011. © 2010 Wiley‐Liss, Inc.     

Drug‐binding energetics of human α‐1‐acid glycoprotein assessed by isothermal titration calorimetry and molecular docking simulations

This study utilizes sensitive, modern isothermal titration calorimetric methods to characterize the microscopic thermodynamic parameters that drive the binding of basic drugs to α‐1‐acid glycoprotein (AGP) and thereby rationalize the thermodynamic data in relation to docking models and crystallographic structures of the drug–AGP complexes. The binding of basic compounds from the tricyclic antidepressant series, together with miaserine, chlorpromazine, disopyramide and cimetidine, all displayed an exothermically driven binding interaction with AGP. The impact of protonation/deprotonation events, ionic strength, temperature and the individual selectivity of the A and F1*S AGP variants on drug‐binding thermodynamics was characterized. A correlation plot of the thermodynamic parameters for all of the test compounds revealed that an enthalpy–entropy compensation is in effect. The exothermic binding energetics of the test compounds were driven by a combination of favorable (negative) enthalpic (?Hº) and favorable (positive) entropic (?Sº) contributions to the Gibbs free energy (?Gº). Collectively, the data imply that the free energies that drive drug binding to AGP and its relationship to drug serum residency evolve from the complex interplay of enthalpic and entropic forces from interactions with explicit combinations of hydrophobic and polar side‐chain sub‐domains within the multi‐lobed AGP ligand binding cavity.Copyright © 2012 John Wiley & Sons, Ltd.     

Hypofolins A – L,ent‐Labdane Diterpenoids from the Roots of Hypoestes phyllostachya ‘Pink Splash’

Twelve new ent‐labdane diterpenoids, hypofolins A – F ( 1 – 6 ) and hypofolins G – L ( 7a / 7b , 8a / 8b , and 9a / 9b ), were isolated from the roots of Hypoestes phyllostachya ‘Pink Splash’. Their structures were elucidated by extensive 1D‐ and 2D‐NMR spectroscopic and HR‐MS data. The absolute configurations of 1 , 2 , 5 , and 7a / 7b were determined by single crystal X‐ray diffraction and ECD analysis, as well as chemical transformations. Compounds 7a / 7b , 8a / 8b , and 9a / 9b were isolated as three pairs of interconverting mixture of two isomers between ketone and hemiketal types. Compound 1 showed weak cytotoxicity against SMMC‐7721 cell line with IC₅₀ value of 31.40 μm .     

11α‐Ethoxy‐β‐boswellic Acid and Nizwanone,a New Boswellic Acid Derivative and a New Triterpene,Respectively, from Boswellia sacra

A new boswellic acid derivative, 11α‐ethoxy‐β‐boswellic acid (EBA; 1 ) and a new ursane‐type triterpene, named nizwanone ( 2 ), were isolated from Omani frankincense Boswellia sacra Flueck . together with two known compounds papyriogenin B and rigidenol. The structures of 1 and 2 were elucidated by detailed spectroscopic analysis using ¹H‐ and ¹³C‐NMR, ¹H,¹H‐COSY, HMQC, HMBC, and HR‐EI‐MS techniques. The relative configurations of 1 and 2 were assigned by comparative analysis of the NMR spectral data with those of known analogs together with NOESY experiments. Structures of known compounds were identified by comparison with the reported data.     

α‐Glucosidase Inhibitory Xanthones from the Roots of Garcinia fusca

Two new compounds, fuscaxanthones J ( 1 ) and K ( 2 ), together with eight known xanthones ( 3 – 10 ) were isolated from an ethyl acetate extract of the roots of Garcinia fusca. Their structures were determined using spectroscopic methods, mainly 1D‐ and 2D‐NMR. α‐Glucosidase inhibitory activity of the isolated compounds was evaluated and fuscaxanthone J ( 1 ) showed the most significant effect with an IC₅₀ value of 8.3 ± 1.8 μm (compared with acarbose, IC₅₀ = 214.5 ± 2.3 μm ).     

4α‐Acetoxyamijidictyol – A New Antifeeding Dolastane Diterpene from the Brazilian Brown Alga Canistrocarpus cervicornis

Chemical investigation of the CH₂Cl₂ crude extract from the brown alga Canistrocarpus cervicornis (Dictyotaceae) led to isolation of one new ( 1 ) and four previously reported dolastane diterpenes ( 2 – 5 ). Their structures were characterized by 1D‐ and 2D‐NMR spectroscopic techniques, including a full single crystal X‐ray diffraction analysis for 1, 2 , and 4 . In addition, the new structure 1 was assayed as chemical defense inhibiting the feeding by the sea urchin Lytechinus variegatus. This study constitutes an additional report broadening the known spectrum of action and defensive roles of secondary metabolites of the C. cervicornis and Dictyotales species.     

Production of 3‐Fucosyllactose in Engineered Escherichia coli with α‐1,3‐Fucosyltransferase from Helicobacter pylori

3‐Fucosyllactose (3‐FL), one of the major oligosaccharides in human breast milk, is produced in engineered Escherichia coli. In order to search for a good α‐1,3‐fucosyltransferase, three bacterial α‐1,3‐fucosyltransferases are expressed in engineered E. coli deficient in β‐galactosidase activity and expressing the essential enzymes for the production of guanosine 5′‐diphosphate‐l ‐fucose, the donor of fucose for 3‐FL biosynthesis. Among the three enzymes tested, the fucT gene from Helicobacter pylori National Collection of Type Cultures 11637 gives the best 3‐FL production in a simple batch fermentation process using glycerol as a carbon source and lactose as an acceptor. In order to use glucose as a carbon source, the chromosomal ptsG gene, considered the main regulator of the glucose repression mechanism, is disrupted. The resulting E. coli strain of ?LP‐YA+FT shows a much lower performance of 3‐FL production (4.50 g L^?1) than the ?L‐YA+FT strain grown in a glycerol medium (10.7 g L^?1), suggesting that glycerol is a better carbon source than glucose. Finally, the engineered E. coli ?LW‐YA+FT expressing the essential genes for 3‐FL production and blocking the colanic acid biosynthetic pathway (?wcaJ) exhibits the highest concentration (11.5 g L^?1), yield (0.39 mol mol^?1), and productivity (0.22 g L^?1 h) of 3‐FL in glycerol‐limited fed‐batch fermentation.     

Pulsatilla decoction and its active ingredients inhibit secretion of NO,ET‐1, TNF‐α, and IL‐1α in LPS‐induced rat intestinal microvascular endothelial cells

To investigate the pharmacological mechanism of the traditional Chinese medicine, Pulsatilla decoction (PD), the levels of nitric oxide (NO), endothelin‐1 (ET‐1), tumor necrosis factor‐α (TNF‐α), and interleukin‐1α (IL‐1α) secreted by cultured rat intestinal microvascular endothelial cells (RIMECs) were determined after treatment with PD and its seven active ingredients, namely anemoside B₄, anemonin, berberine, jatrorrhizine, palmatine, aesculin, and esculetin. RIMECs were challenged with lipopolysaccharide (LPS) at 1 µg ml^?1 for 3 h and then treated with PD at 1, 5, and 10 mg ml^?1 and its seven ingredients at 1, 5, and 10 µg ml^?1 for 21 h, respectively. The results revealed that PD, anemonin, berberine, and esculetin inhibited the production of NO; PD, anemonin, and esculetin inhibited the secretion of ET‐1; PD, anemoside B₄, berberine, jatrorrhizine, and aesculin downregulated TNF‐α expression; PD, anemoside B₄, berberine, and palmatine decreased the content of IL‐1α. It showed that PD and its active ingredients could significantly inhibit the secretion of NO, ET‐1, TNF‐α, and IL‐1α in LPS‐induced RIMECs and suggested they would reduce inflammatory response via these cytokines. Copyright © 2009 John Wiley & Sons, Ltd.     

The impact of β‐azido(or 1‐piperidinyl)methylamino acids in position 2 or 3 on biological activity and conformation of dermorphin analogues

The synthesis of new dermorphin analogues is described. The (R)‐alanine or phenylalanine residues of natural dermorphin were substituted by the corresponding α‐methyl‐β‐azidoalanine or α‐benzyl‐β‐azido(1‐piperidinyl)alanine residues. The potency and selectivity of the new analogues were evaluated by a competitive receptor binding assay in rat brain using [³H]DAMGO (a μ ligand) and [³H]DELT (a δ ligand). The most active analogue in this series, Tyr‐(R)‐Ala‐(R)‐α‐benzyl‐β‐azidoAla‐Gly‐Tyr‐Pro‐Ser‐NH₂ and its epimer were analysed by ¹H and ¹³C NMR spectroscopy and restrained molecular dynamics simulations. The dominant conformation of the investigated peptides depended on the absolute configuration around C^α in the α‐benzyl‐β‐azidoAla residue in position 3. The (R) configuration led to the formation of a type I β‐turn, whilst switching to the (S) configuration gave rise to an inverse β‐turn of type I′, followed by the formation of a very short β‐sheet. The selectivity of Tyr‐(R)‐Ala‐(R) and (S)‐α‐benzyl‐β‐azidoAla‐Gly‐Tyr‐Pro‐Ser‐NH₂ was shown to be very similar; nevertheless, the two analogues exhibited different conformational preferences. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.     

Antibacterial Δ1‐3‐Ketosteroids from the South China Sea Gorgonian Coral Subergorgia rubra

Three new Δ¹‐3‐ketosteroids characterized with a 9‐OH, subergosterones A–C ( 1 – 3 ), together with five known analogs 4 – 8 , were obtained from the gorgonian coral Subergorgia rubra collected from the South China Sea. The structures of 1 – 3 , including their absolute configurations, were determined by comprehensive spectroscopic methods and electronic circular dichroism (ECD) experiments. Compounds 2 and 3 exhibited inhibitory antibacterial activities against Bacillus cereus with MIC values of 1.56 μM .