Cytochrome P450s are heme-containing monooxygenases that require electron transfer proteins for their catalytic activities. They prefer hydrophobic compounds as substrates and it is, therefore, desirable to perform their reactions in non-aqueous media. Reversed micelles can stably encapsulate proteins in nano-scaled water pools in organic solvents. However, in the reversed micellar system, when multiple proteins are involved in a reaction they can be separated into different micelles and it is then difficult to transfer electrons between proteins. We show here that an artificial self-sufficient cytochrome P450, which is an enzymatically crosslinked fusion protein composed of P450 and electron transfer proteins, showed micelle-size dependent catalytic activity in a reversed micellar system. Furthermore, the presence of thermostable alcohol dehydrogenase promoted the P450-catalyzed reaction due to cofactor regeneration. Full article

A series of fluorescent sensors based on 8-hydroxyquinoline dansylate as core and dendritic PAMAM as shell were synthesized. Their fluorescence characteristic and fluorescent sensing behavior toward metal ions were studied in water/methanol (1: 1, v/v). The sensors exhibit good selectivity and sensitivity for Fe³⁺ ion and to some extent for Cr³⁺ ion. The third generation dendrimer has the better sensitivity than the first and second generations. Full article

N-Methyl-3-acylpyrroles were synthesized via a multicomponent reaction of dimethylacetylene dicarboxylate (DMAD), N-methylhydroxylamine and acylchlorides in the presence of KHCO₃. For comparison both conventional and microwave protocols were examined in this procedure. The reaction is clean and gives the products in good to excellent yields under conventional heating conditions at 40 ºC in anhydrous dichloromethane. Full article

Ultraviolet-B (UV-B) radiation is harmful to plants and human beings. Many secondary metabolites, like flavonoids, alkaloids, and lignin, are UV-B absorbing compounds, which can protect the genetic material of plants. Furthermore, they are active components of herbal drugs. UV-B radiation can activate the self-protective secondary metabolism system. The results of this paper provide a method to induce bioactive secondary metabolites from mulberry leaves (Morus alba L.) by UV-B irradiation in vitro. Five significantly different chromatographic peaks were found by HPLC fingerprint after induction, from which two active compounds were identified: One was chalcomoracin, a natural Diels-Alder type adduct with antibacterial activity; the other one was moracin N, which is a precursor of chalcomoracin. Their contents were 0.818 mg/g and 0.352 mg/g by dry weight, respectively. Full article

The work describes a study of the oxidation power of N-doped and undoped anatase TiO₂, as well as TiO₂ Degussa P25 suspensions for photocatalytic degradation of the herbicides RS-2-(4-chloro-o-tolyloxy)propionic acid (mecoprop) and 3,6-dichloro-pyridine-2-carboxylic acid (clopyralid) using visible and UV light. Undoped nanostructured TiO₂ powder in the form of anatase was prepared by a sol-gel route. The synthesized TiO₂, as well as TiO₂ Degussa P25 powder, were modified with urea to introduce nitrogen into the structure. N-doped TiO₂ appeared to be somewhat more efficient than the starting TiO₂ (anatase) powder when visible light was used for mecoprop degradation. N-doped TiO₂ Degussa P25 was also slightly more efficient than TiO₂ Degussa P25. However, under the same experimental conditions, no degradation of clopyralid was observed in the presence of any of the mentioned catalysts. When the kinetics of mecoprop degradation was studied using UV light, more efficient were the undoped powders, while in the case of clopyralid, N-doped TiO₂ Degussa P25 powder was most efficient, which is probably a consequence of the difference in the molecular structure of the two herbicides. Full article

The calpain inhibitor MDL-28710 blocks the early local pro-inflammatory cytokine gene expression in mice after chronic constriction nerve injury (CCI). One-hundred-thirteen wild type mice of C57Bl/6J background received CCI of the right sciatic nerve. Mechanical paw withdrawal thresholds and thermal withdrawal latencies were investigated at baseline and at 1, 3, and 7 days after CCI. Three application regimens were used for MDL-28170: a) single injection 40 min before CCI; b) serial injections of MDL-28170 40 min before and up to day three after CCI; c) sustained application via intraperitoneal osmotic pumps. The control animals received the vehicle DMSO/PEG 400. The tolerable dose of MDL-28170 for mice was 30 mg/kg body weight, higher doses were lethal within the first hours after application. Mechanical withdrawal thresholds and thermal withdrawal latencies were reduced after CCI and did not normalize after single or serial injections, nor with application of MDL-28170 via osmotic pumps. Although the calpain inhibitor MDL-28170 inhibits the early local cytokine upregulation in the sciatic nerve after CCI, pain behavior is not altered. This finding implies that local cytokine upregulation after nerve injury alone is only one factor in the induction and maintenance of neuropathic pain. Full article

One pot synthesis of 1-arylpyrazolo[3,4-d]pyrimidin-4-ones by the reaction of 5-amino-N-substituted-1H-pyrazole-4-carbonitrile with different lower aliphatic acids in the presence of POCl₃has been developed_. The structures of all the title compounds have been confirmed by IR, ¹H-NMR, ^13C-NMR, and elemental analyses. Moreover, the structures of one of these compounds, 2c, was confirmed by single-crystal X-ray diffraction. Full article

This article deal with the parallel synthesis of a 96 product-sized library using a polymer-based copper catalyst that we developed which can be easily separated from the products by simple filtration. This gave us the opportunity to use this catalyst in an automated chemical synthesis station (Chemspeed ASW-2000). Studies and results about the preparation of the catalyst, its use in different solvent systems, its recycling capabilities and its scope and limitations in the synthesis of this library will be addressed. The synthesis of the triazole library and the very good results obtained will finally be discussed. Full article

Two isomeric N-(methoxycarbonylthienylmethyl)thioureas were synthesised by a sequence of radical bromination of methylthiophenecarboxylic esters, substitution with trifluoroacetamide anion, deprotection, formation of the corresponding isothiocyanates and addition of ammonia. The interaction of these new thiophene-based thioureas with inducible and neuronal nitric oxide synthase was evaluauted. These novel thienylmethylthioureas stimulated the activity of inducible Nitric Oxide Synthase (iNOS). Full article

An efficient synthesis of a methyl derivative of the indoloquinoline alkaloid cryptosanguinolentine based on microwave-assisted reactions is described. The microwave-assisted synthesis of an intermediate 4-hydroxy-2-methylquinoline yielded 86% of the desired product and other intermediates prepared yielded high % of products in shorter reaction times, under optimum conditions, as compared to traditional methods. Full article

The aim of this study was to evaluate the antimicrobial activity of Wuyiencin fractions with different polarities against six indicator microorganisms: Rhodotorula rubra, Bacillus subtilis, Bacillus megaterium, Escherichia coli, Cladosporium fulvum and Staphylococcus aureus. The fermentation broth of Wuyiencin was submitted to AB-8 macroporous adsorptive resin and fractionated with solvents of different polarity. The fraction eluted with water had remarkably antimicrobial activity against all the microorganisms investigated except for C. fulvum and S. aureus (MIC ≤ 0.0625 mg/mL), probably due to the presence of active components. The fraction eluted with methanol showed potential antimicrobial activity against all the test microorganisms except for R.rubra, with MIC values of0.5 and 2 mg/mL. In conclusion, fractions eluted with water and methanol, respectively, represent the main active-part of Wuyiencin, and could be emphasized for agricultural applications in the future. Full article

Ethnopharmacological relevance:Elaeis guineensisJacq (Arecaceae) is one of the plants that are central to the lives of traditional societies in West Africa. It has been reported as a traditional folkloric medicine for a variety of ailments. The plant leaves are also used in some parts of Africa for wound healing, but there are no scientific reports on any wound healing activity of the plant. Aim of the study:To investigate the effects of E. guineensis leaf on wound healing activity in rats. Methods: A phytochemical screening was done to determine the major phytochemicals in the extract. The antimicrobial activity of the extract was examined using the disk diffusion technique and broth dilution method. The wound healing activity of leaves of E. guineensiswas studied by incorporating the methanolic extract in yellow soft paraffin in concentration of 10% (w/w). Wound healing activity was studied by determining the percentage of wound closure, microbial examination of granulated skin tissue and histological analysis in the control and extract treated groups. Results: Phytochemical screening reveals the presence of tannins, alkaloids, steroids, saponins, terpenoids, and flavonoids in the extract. The extract showed significant activity against Candida albicans with an MIC value of 6.25 mg/mL. The results show that the E. guineensis extract has potent wound healing capacity, as evident from better wound closure, improved tissue regeneration at the wound site, and supporting histopathological parameters pertaining to wound healing. Assessment of granulation tissue every fourth day showed a significant reduction in microbial count. Conclusions: E. guineensis accelerated wound healing in rats, thus supporting this traditional use. Full article

Ten essential oils, namely, mint (Mentha spicata L.,Lamiaceae), ginger (Zingiber officinaleRosc.,Zingiberaceae), lemon (Citrus limon Burm.f.,Rutaceae), grapefruit (Citrus paradisi Macf., Rutaceae), jasmine (Jasminum grandiflora L.,Oleaceae), lavender (Mill.,Lamiaceae), chamomile (Matricaria chamomilla L., Compositae), thyme (Thymus vulgaris L., Lamiaceae), rose (Rosa damascena Mill.,Rosaceae) and cinnamon (Cinnamomum zeylanicumN. Lauraceae) were tested for their antibacterial activities towards Propionibacterium acnes and in vitro toxicology against three human cancer cell lines. Thyme, cinnamon and rose essential oils exhibited the best antibacterial activities towards P. acnes, with inhibition diameters of 40 ± 1.2 mm, 33.5 ± 1.5 mm and 16.5 ± 0.7 mm, and minimal inhibitory concentrations of 0.016% (v/v), 0.016% (v/v) and 0.031% (v/v), respectively. Time-kill dynamic procedures showed that thyme, cinnamon, rose, and lavender essential oils exhibited the strongest bactericidal activities at a concentration of 0.25% (v/v), and P. acnes was completely killed after 5 min. The thyme essential oil exhibited the strongest cytotoxicity towards three human cancer cells. Its inhibition concentration 50% (IC₅₀) values on PC-3, A549 and MCF-7 tumor cell lines were 0.010% (v/v), 0.011% (v/v) and 0.030% (v/v), respectively. The cytotoxicity of 10 essential oils on human prostate carcinoma cell (PC-3) was significantly stronger than on human lung carcinoma (A549) and human breast cancer (MCF-7) cell lines. Full article

A series of new mesogenic azomethine diols were successfully synthesized by condensation reactions between various chloroalkanols and N,N'-bis(4-hydroxy)-benzylidene-o-toluidine (1). The structures of these compounds were confirmed by CHN, FT-IR, ¹H-NMR, and ¹³C-NMR spectrophotometer. Their thermotropic liquid crystalline behavior was studied using differential scanning calorimetry (DSC) and polarizing optical microscope (POM). 4,4'-di(4-Hydroxybutoxy)-N-benzylidine-o-tolidine (2a) does not exhibit liquid crystalline properties. A nematic texture was observed for mesogenic diols 2b, and 2d, whereas the diol 2c exhibits a smectic mesophase. The increase of terminal alkyl chain in these mesogenic diols leads to a decrease in the transition temperature. Full article

Cultivation of the endophytic fungus Penicillium commune, which was isolated from the semi-mangrove plant Hibiscus tiliaceus,afforded one new compound 1-O-(2,4-dihydroxy-6-methylbenzoyl)-glycerol (1) along with thirteen known products, including 1-O-acetylglycerol (2), N-acetyltryptophan (3), 3-indolylacetic acid methyl ester (4), 1-(2,4-dihydroxy-3,5-dimethylphenyl)ethanone (5), 2-(2,5-dihydroxyphenyl)acetic acid (6), (4R,5S)-5-hydroxyhexan-4-olide (7), thymidine (8), uracil (9), thymine (10), ergosterol (11), β-sitosterol (12),β-daucosterol (13), and ergosta-7,22-dien-3β,5α,6β-triol (14). The structures of these compounds were established by detailed NMR spectroscopic analysis, as well as by comparison with literature data or with authentic samples. Full article

Arylhydrazonomalononitriles 1a,b react with phenylhydrazine to yield amidrazones 2a,b that cyclize to give 2-aryl-5-phenylhydrazono-2,5-dihydro-[1,2,4]-triazine-6-carbonitriles 5a,b upon reaction with dimethylformamide dimethylacetal (DMFDMA). Refluxing 5a,b in glacial acetic acid resulted in the formation of the pyrazolo-1,2,4-triazines 6a,b. Compounds 6a,b were also formed upon treatment of 3-amino-4-phenylhydrazono-1-phenyl-2-pyrazolin-5-ones 7a,b with DMFDMA. Reacting these triazinyl arylhydrazononitriles 5a,b with hydroxylamine hydrochloride in ethanolic sodium acetate afforded amidrazones 8a,b that are readily cyclized in refluxing dimethylformamide into [1,2,4]triazino[1,2,3]triazines 10a,b. Full article

Catalytic hydrogenation under mild conditions of olefins, unsaturated aldeydes and ketones, nitriles and nitroarenes was investigated, using a supported rhodium complex obtained by copolymerization of Rh(cod)(aaema) [cod: 1,5-cyclooctadiene, aaema–: deprotonated form of 2-(acetoacetoxy)ethyl methacrylate] with acrylamides. In particular, the hydrogenation reaction of halonitroarenes was carried out under 20 bar hydrogen pressure with ethanol as solvent at room temperature, in order to minimize hydro-dehalogenation. The yields in haloanilines ranged from 85% (bromoaniline) to 98% (chloroaniline). Full article

The two heteropolyacids H₃PW₁₂O₄₀ and H₃PMo₁₂O₄₀, and their homologous salts (NH₄)₃PW₁₂O₄₀, and (NH₄)₃PMo₁₂O₄₀ were prepared and tested in the cationic polymerization of styrene. The results showed that the heteropolytungstates were more reactive than the heteropolymolybdates. It has been found that the yield and the viscosity averagemolecular weight (M_v) of polystyrene are directly proportional to the acidity strength of the heteropolyanions (H₃PW₁₂O₄₀ > H₃PMo₁₂O₄₀ > (NH₄)₃PW₁₂O₄₀ > (NH₄)₃PMo₁₂O₄₀). The highest yield (68.0%) and M_v (7,930) were obtained by using H₃PW₁₂O₄₀. In addition, H₃PW₁₂O₄₀ polymerized the styrene under mild conditions and was recyclable, and could behave as a truly heterogeneous catalyst. Full article

Colorectal cancer (CRC) is a major cause of tumor-related morbidity and mortality worldwide. Recent research suggests that pharmacological intervention using dietary factors that activate the redox sensitive Nrf2/Keap1-ARE signaling pathway may represent a promising strategy for chemoprevention of human cancer including CRC. In our search for dietary Nrf2 activators with potential chemopreventive activity targeting CRC, we have focused our studies on trans-cinnamic aldehyde (cinnamaldeyde, CA), the key flavor compound in cinnamon essential oil. Here we demonstrate that CA and an ethanolic extract (CE) prepared from Cinnamomum cassia bark, standardized for CA content by GC-MS analysis, display equipotent activity as inducers of Nrf2 transcriptional activity. In human colon cancer cells (HCT116, HT29) and non-immortalized primary fetal colon cells (FHC), CA- and CE-treatment upregulated cellular protein levels of Nrf2 and established Nrf2 targets involved in the antioxidant response including heme oxygenase 1 (HO-1) and γ-glutamyl-cysteine synthetase (γ-GCS, catalytic subunit). CA- and CE-pretreatment strongly upregulated cellular glutathione levels and protected HCT116 cells against hydrogen peroxide-induced genotoxicity and arsenic-induced oxidative insult. Taken together our data demonstrate that the cinnamon-derived food factor CA is a potent activator of the Nrf2-orchestrated antioxidant response in cultured human epithelial colon cells. CA may therefore represent an underappreciated chemopreventive dietary factor targeting colorectal carcinogenesis. Full article

Allergies are highly complex disorders with clinical manifestations ranging from mild oral, gastrointestinal, recurrent wheezing, and cutaneous symptoms to life-threatening systemic conditions. The levels of arachidonic acid, eicosanoids, histamine, organic acids and valine are considered to have a variety of physiological functions in connection with allergies. In this research, we have developed a RP-LC/MS method to separate and quantitate six different potential endogenous biomarkers, including leukotrieneB₄ (LTB₄), prostaglandinD₂ (PGD₂), arachidonic acid (AA), histamine (HI), lactic acid (LA) and valine (VAL), from serum of rats with ovalbumin (OVA)-induced allergy and normal rats, and the discrepancies between the model group and the control group were compared. The separation was performed on a Prevail C18 column (250 mm × 4.6 mm, 5 μm) with a gradient elution of acetonitrile with 0.1% formic acid (v/v) and 10 mM ammonium formate (adjusted to pH 4.0 with formic acid) at a flow rate of 0.5 mL min⁻¹ The method was validated and shown to be sensitive, accurate (recovery values 76.16–92.57%) and precise (RSD < 10% for all compounds) with a linear range over several orders of magnitude. The method was successfully applied to rat serum and shown to be indicative of the endogenous levels of biomarkers within the rat body. The analysis of the biomarkers can provide insight into the allergic mechanisms associated with related diseases. Full article

The reaction of intracomplex proton transfer (44BPY^-....HO-H) ® 44BPYH^. + OH^- that follows the photoreduction of 4,4’-bipyridine (44BPY) into its anion radical 44BPY^- in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) is investigated in acetonitrile-water mixtures by using picosecond transient absorption. The dependence of the appearance kinetics of the 44BPYH^. radical on the water content reveals a highly diffusional proton transfer process that is controlled by the dynamics of solvation of the released hydroxide ion. The results are interpreted on the basis of a two-step mechanism where an intermediate solvation complex (44BPYH^.)OH^-(H₂O)₃ is formed first before evolving toward a final four-water hydration structure OH^-(H₂O)₄. Full article

The in vitro and in vivo antioxidant activities of different extracts of laurel leaves were studied. Free radical scavenging capacity (RSC) was evaluated measuring the scavenging activity on the DPPH, NO, O₂^·- and OH radicals. The effects on lipid peroxidation (LP) were also evaluated. Experimental results indicate that ethyl acetate extract of leaves has exhibited the largest RSC capacity in neutralization of DPPH, NO, O₂^·- and OH radicals. The same result was obtained in investigation of extracts impact on LP. The in vivo effects were evaluated on some antioxidant systems (activities of GSHPx, LPx, Px, CAT and XOD, and GSH content) in the mice liver and blood-hemolysate after treatment with the examined laurel extracts, or in combination with carbon tetrachloride (CCl₄). On the basis of the results obtained it can be concluded that the examined extracts exhibited a certain protective effect, which is more pronounced on the liver than on blood-hemolysate parameters. The results obtained indicate toxicity of CCl₄, probably due to the radicals involved in its metabolism. Combined treatments with CCl₄ and the examined extracts showed both positive and negative synergism. Based on the experimental results, the strongest protective effect was shown by the EtOAc extract. Full article

Helichrysum plicatum (Turkish Helichrysum) has been used in folk medicine for the treatment of gastric and hepatic disorders. The aim of the present study was to examine the relaxant activity of an extract of H. plicatum flowers on isolated rat ileum. Segments of ileum of rats were suspended in an organ bath. Cumulative concentrations of H. plicatum ethanol extract induced a relaxant effect on spontaneous rat ileum contractions. H. plicatum extract caused a mean contractile response of 81.68 ± 6.17% (at a dose of 0.01 mg/mL) and 30.08 ± 9.07% (at a dose of 1 mg/mL). A similar effect was observed with papaverine (0.01–3 μg/mL). H. plicatum extract (0.01–1 mg/mL) relaxed high K⁺ (80 mM) precontractions, an effect similar to that caused by papaverine (0.01–3 μg/mL). The plant extract (0.03–0.3 mg/mL) also induced a significant depression of the cumulative concentration response curve for acetylcholine (5–1500 nM) (p < 0.01). Atropine (140 nM) abolished the acetylcholine effect. The extract (0.03–0.3 mg/mL) reduced the histamine (1–300 nM) and BaCl₂ (3–900 μM) induced contractions (p < 0.01). Our results showed the relaxant effect of the ethanol extract of Helichrysum plicatum flowers on the isolated rat intestine Extract of H. plicatum can inhibit the spontaneous ileum contractions and contractions induced by acetylcholine, histamine, barium and potassium ions. Full article

Quality control standardizations of the various medicinal plants used in traditional medicine is becoming more important today in view of the commercialization of formulations based on these plants. An attempt at standardization of Cassia spectabilis leaf has been carried out with respect to authenticity, assay and chemical constituent analysis. The authentication involved many parameters, including gross morphology, microscopy of the leaves and functional group analysis by Fourier Transform Infrared (FTIR) spectroscopy. The assay part of standardization involved determination of the minimum inhibitory concentration (MIC) of the extract which could help assess the chemical effects and establish curative values. The MIC of the C. spectabilis leaf extracts was investigated using the Broth Dilution Method. The extracts showed a MIC value of 6.25 mg/mL, independent of the extraction time. The chemical constituent aspect of standardization involves quantification of the main chemical components in C. spectabilis. The GCMS method used for quantification of 2,4-(1H,3H)-pyrimidinedione in the extract was rapid, accurate, precise, linear (R² = 0.8685), rugged and robust. Hence this method was suitable for quantification of this component in C. spectabilis. The standardization of C. spectabilis is needed to facilitate marketing of medicinal plants, with a view to promoting the export of valuable Malaysian Traditional Medicinal plants such as C. spectabilis. Full article

In this study, the flavor substances of soypaste were extracted by a simultaneous distillation method and identified by GC-MS. The characteristic aroma components of soypaste were determined by the GC-O technique and the FD value of the characteristic aroma components was determined by AEDA method. It could be inferred that the aroma of the soypaste should be attributed to the presence of heterocyclic compounds and organic acids, with the heterocyclic compounds playing a prominent role. Full article

The enantioselective hydrogenation of 1-phenyl-1,2-propanedioneover Pt colloids stabilized with (R,S)-4,5-dihydro-4,5-diphenyl-2-(6-cyanopyridinyl)imidazoline (CI) supported on a meso-structured ZrO₂ under a pressure of 40 bar of H₂ at 298 K has been investigated_. The metal loading in all catalysts was 1 wt%. The effect of the amount of chiral modifier on the metal particle size and on the catalytic behavior was analyzed. It was found that as the CI/Pt molar ratio increases from 2.5 to 3.5 the Pt crystal size decreases from 3.0 to 1.8 nm. All catalysts were very active in the studied reaction, with the most active one being the catalyst with smaller Pt particles, whereas the selectivity is higher in those catalysts with larger chiral modified Pt metal particles. Full article

A brief summary of selected pioneering and mechanistic contributions in the field of carbon-carbon cross-coupling reactions with palladium nanoparticles (Pd-NPs) in ionic liquids (ILs) is presented. Five exemplary model systems using the Pd-NPs/ILs approach are presented: Heck, Suzuki, Stille, Sonogashira and Ullmann reactions which all have in common the use of ionic liquids as reaction media and the use of palladium nanoparticles as reservoir for the catalytically active palladium species. Full article

The reactions of selected α,β-unsaturated steroidal ketones with Lawesson’s reagent (LR) in CH₂Cl₂ and toluene under the standard reaction conditions and with a combination of phosphorus pentasulfide with hexamethyldisiloxane (P₄S₁₀/HMDO) in 1,2-dichlorobenzene (ODCB) under microwave irradiation were investigated and for this purpose several cholestane, androstane and pregnane carbonyl derivatives were chosen. Depending on the reagent and the solvent, 19 new sulfur containing compounds, including dithiones 4c and 4d, α,β-unsaturated 3-thiones 3a-e, dimer-sulfides 2a-e, 1,2,4-trithiolanes 5a-e and phosphonotrithioates 6b-e were synthesized. All newly prepared compounds were characterized by IR, ¹H- and ¹³C-NMR spectroscopy and elemental analysis. Full article

In this study, we investigated the antifungal activity and mechanism of action of (+)-pinoresinol, a biphenolic compound isolated from the herb Sambucus williamsii,used in traditional medicine. (+)-Pinoresinol displays potent antifungal properties without hemolytic effects on human erythrocytes. To understand the antifungal mechanism of (+)-pinoresinol, we conducted fluorescence experiments on the human pathogen Candida albicans. Fluorescence analysis using 1,6-diphenyl-1,3,5-hexatriene (DPH) indicated that the (+)-pinoresinol caused damage to the fungal plasma membrane. This result was confirmed by using rhodamine-labeled giant unilamellar vesicle (GUV) experiments. Therefore, the present study indicates that (+)-pinoresinol possesses fungicidal activities and therapeutic potential as an antifungal agent for the treatment of fungal infectious diseases in humans. Full article

Aromatase represents an important target for the treatment of hormone-dependent breast cancer. In the present study, nine alkaloids from the dichloromethane extract of Corydalis yanhusuo were identified by liquid chromatography tandem mass spectrometry (LC-MS/MS) and tested for their aromatase binding activities using an ultrafiltration LC-MS method by investigating the differences of peak areas of compounds before and after incubations with aromatase. It was demonstrated that the quaternary protoberberine alkaloids and the tertiary protoberberine alkaloids exhibited potent aromatase binding activities. The quaternary ammonium group and the methyl group at C-13 position of tertiary protoberberine alkaloids might be necessary for the activity. The findings should provide guidance for the discovery of potential aromatase inhibitors from natural products. Full article

Phenolic compounds are present at very high concentrations in the bark of Acacia mangium. These compounds are known to have strong antioxidant activity and thus different beneficial effects on human health. Phenolic compounds in bark of A. mangium were extracted and their antioxidant activities were investigated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging and ferric-reducing antioxidant power (FRAP) assays. A central composite design has been employed to optimize the experimental conditions for a high total phenolic content and antioxidant activity. The desirability function approach has been employed to simultaneously optimize the three responses: total phenols, antiradical activity and FRAP. An extraction time of 90 min, liquid-solid ratio of 5, and temperature of 50 °C was predicted for the optimum experimental conditions using the desirability function. A significant linear relationship between antioxidant potency, antiradical activity and the content of phenolic compounds of bark extracts was observed. The structures of condensed tannins isolated from A. mangium were characterized by MALDI-TOF MS analyses. Condensed tannin oligomers from A. mangium were shown to be heterogeneous mixtures consisting of procyanidin and prodelphinidin structural units with polymerization degrees up to 9. Full article

The effects of Andrographis paniculata and Orthosiphon stamineus extracts on the in vitro glucuronidation of 4-methylumbelliferone (4MU) by recombinant human UGTs, UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A10, UGT2B7 and UGT2B15 were determined. The potential inhibitory effects of both of the extracts on the activity of each of the UGT isoforms were investigated using 4MU as the substrate. Incubations contained UDP-glucuronic acid (UDPGA) as the cofactor, MgCl₂, cell lysate of respective isoform, and 4MU at the approximate apparent K_m or S₅₀ value of each isoform. Final concentrations of Andrographis paniculata and Orthosiphon stamineus extracts used were 0.025, 0.25, 2.5, 25 and 50 μg/mL and 0.01, 0.10, 1.0, 10 and 50 μg/mL respectively. Both extracts variably inhibited the activity of most of the isoforms in a concentration dependent manner. Andrographis paniculata extract was the better inhibitor of all the isoforms studied (IC₅₀ 1.70 μg/mL for UGT1A3, 2.57 μg/mL for UGT1A8, 2.82 μg/mL for UGT2B7, 5.00 μg/mL for UGT1A1, 5.66 μg/mL for UGT1A6, 9.88 μg/mL for UGT1A7 and 15.66 μg/mL for UGT1A10). Both extracts showed less than 70% inhibition of UGT2B15, so the IC₅₀ values were >50μg/mL. The inhibition of human UGTs by Andrographis paniculata and Orthosiphon stamineus extracts in vitro suggests a potential for drug-herbal extract interactions in the therapeutic setting. Full article

New approaches for the synthesis of hydrazide-hydrazone derivatives were demonstrated as well as some heterocyclizations of such derivatives to afford 1,3,4-triazine, pyridine and 1,3,4-oxadiazine derivatives. The antitumor evaluation of the newly synthesized products against three cancer cell lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) were recorded. Most of the synthesized compounds showed high inhibitory effects. Full article

An investigation into the potential ruthenium(II) 1-3 complexes of type [RuCl₂(P)₂(N)₂] using triphenylphosphine and 1,3-bis-diphenylphosphinepropane and 3-(triethoxysilyl)propylamine has been carried out at room temperature in dichloromethane under an inert atmosphere. The structural behaviors of the phosphine ligands in the desired complexes during synthesis were monitored by ³¹P{¹H}-NMR. The structure of complexes 1-3 described herein has been deduced from elemental analyses, infrared, FAB-MS and ¹H-, ¹³C- and ³¹P-NMR spectroscopy. Xerogels X1-X3 were synthesized by simple sol-gel process of complexes 1-3 using tetraethoxysilane as co-condensation agent in methanol/THF/water solution. Due to their lack of solubility, the structures of X1-X3 were determined by solid state ¹³C-, ²⁹Si- and ³¹P-NMR spectroscopy, infrared spectroscopy and EXAFS. Full article

1,2-bis(2-methylallyl)disulfane was synthesized from sodium sulfide and 3-chloro-2-methylpropylene. The structure of the target product was confirmed by GC-MS, 1H-NMR and elemental analysis. Cell viability assay, flow-cytometric analysis and protein expression results showed that 1,2-bis(2-methylallyl)disulfane could significantly inhibit the proliferation, and induce the apoptosis of human HepG2 cells. Full article

The impact of immobilization of oxazaborolidines supported on silica via different substituents on the boron and nitrogen atoms is evaluated in the enantioselective reduction of acetophenone. The performances of the homogeneous analog oxazaborolidines and silica supported-ones are compared by varying different parameters. This article deals with the synthesis, characterization and catalytic evaluation of silica-supported oxazaborolidines, their recycling capabilities and regeneration limitations. Full article

This work presents a new synthetic approach to aromatic and aliphatic polycarbonates by melt polycondensation of bisphenol A diacetates with alkylene- and arylenediphenyl dicarbonates. The diphenyl dicarbonates were prepared from phenyl chloroformate and the corresponding dihydroxy compounds. The process involved a precondensation step under a slow stream of dry argon with the elimination of phenyl acetate, followed by melt polycondensation at high temperature and under vacuum. The potential of this reaction is demonstrated by the successful synthesis of a series of aromatic-aromatic and aromatic-aliphatic polycarbonates having inherent viscosities from 0.19 to 0.43 dL/g. Thus low to intermediate molecular mass polymers were obtained. The ¹³C-NMR spectra of the carbon of the carbonate group showed that the formed polycarbonates contain partial random sequence distribution of monomer residues in their chains. The polycarbonates were characterized by inherent viscosity, FTIR, ¹H-NMR and ¹³C-NMR spectroscopy. The glass transition temperatures, measured by DSC, of the polycarbonates were in the range 13–108 ºC. The thermogravimetric curves of showed that these polymers have good thermal stability up to 250 ºC. The present approach may open the door for novel polycarbonates containing other organic functional groups. Full article

The essential oils of the Osmanthus fragrans tea (OFT), Osmanthus fragrans (OF) and green tea (GT) had been extracted by steam distillation and analyzed by gas chromatography-mass spectrometry (GC-MS) with the help of heuristic evolving latent projections (HELP), an effective chemometric resolution method (CRM). The overlapping peak clusters were resolved into pure chromatograms and pure mass spectra with HELP. The qualitative analysis was performed by similarity searches in the National Institute of Standards and Technology (NIST) mass spectra database with the obtained pure mass spectrum of each component. Identification of some compounds was also assisted by comparison of temperature-programmed retention indices (PTRI) with authentic standards included in our own laboratory database under construction. The quantitative results were obtained by overall volume integration (OVI) method. A total of 67, 73 and 53 components in essential oils of the OFT, OF and GT were identified, accounting for 90.83%, 93.65% and 89.97% total contents of the essential oil of OFT, OF and GT, respectively. Full article

Response surface methodology was employed to optimize the conditions for alkaline extraction of polysaccharides from Ganoderma lucidum. The results indicated that the optimum conditions were an extraction temperature of 60.1 ºC, an extraction time of 77.3 min, a sodium hydroxide (NaOH) concentration of 5.1% and a substrate/liquid ratio of 1:21.4. Immunological assays results have shown that the alkaline soluble polysaccharides have no noticeable effects on monocyte phagocytosis and immune organ (spleen, thymus) weight of of immunocompromised mice at the tested dosages. However, they could restore delayed type hypersensitivity reaction to dinitrofluorobenzene (DFNB), hemolysis antibody levels at the three doses applied, and improve the natural killer cell activity at the high-dose and medium dose. Full article

Cu(II) complexes with asymmetrical and symmetrical porphyrinic ligands were synthesized with superior yields using microwave irradiation. The paper presents the synthesis of 5-(3-hydroxyphenyl)-10,15,20-tris-(4-carboxymethylphenyl)-21,23-Cu(II)-porphine in comparison to its symmetrical complex 5,10,15,20-meso-tetrakis-(4-carboxy-methylphenyl)-21,23-Cu(II) porphine. The two compounds were characterized by FT-IR, UV–Vis and EPR spectroscopy, which fully confirmed the structures. The spectral molecular absorption properties of the porphyrinic complexes were studied in organic solvents (methanol, ethanol, iso-propanol, dimethyl sulfoxide, dimethylformamide and methylene chloride), and the influence of the solvent polarity on the absorbance maxima is described. In order to establish their future potential in biomedical applications preliminary toxicological studies consisting of viability and proliferation of standard tumor cell lines (MCF7 and B16) testing was performed. The obtained results indicate a low toxicity for both compounds and further recommends them for testing in light activation protocols. Full article

Two samples of oak honeydew honey were investigated. Headspace solid-phase microextraction (HS-SPME) combined with GC and GC/MS enabled identification of the most volatile organic headspace compounds being dominated by terpenes(mainly cis- and trans-linalool oxides). The volatile and less-volatile organic composition of the samples was obtained by ultrasonic assisted extraction (USE) with two solvents (1:2 (v/v) pentane -diethyl ether mixture and dichloromethane) followed by GC and GC/MS analysis. Shikimic pathway derivatives are of particular interest with respect to the botanical origin of honey and the most abundant was phenylacetic acid (up to 16.4%). Antiradical activity (DPPH assay) of the honeydew samples was 4.5 and 5.1 mmol TEAC/kg. Ultrasonic solvent extracts showed several dozen times higher antiradical capacity in comparison to the honeydew. Antioxidant capacity (FRAP assay) of honeydew samples was 4.8 and 16.1 mmol Fe²⁺/kg, while the solvent mixture extracts showed antioxidant activity of 374.5 and 955.9 Fe²⁺/kg, respectively, and the dichloromethane extracts 127.3 and 101.5 mmol Fe²⁺/kg. Full article

The tissue-nonspecific alkaline phosphatase (TNAP) isozyme is centrally involved in the control of normal skeletal mineralization and pathophysiological abnormalities that lead to disease states such as hypophosphatasia, osteoarthritis, ankylosis and vascular calcification. TNAP acts in concert with the nucleoside triphosphate pyrophosphohydrolase-1 (NPP1) and the Ankylosis protein to regulate the extracellular concentrations of inorganic pyrophosphate (PP_i), a potent inhibitor of mineralization. In this review we describe the serial development of two miniaturized high-throughput screens (HTS) for TNAP inhibitors that differ in both signal generation and detection formats, but more critically in the concentrations of a terminal alcohol acceptor used. These assay improvements allowed the rescue of the initially unsuccessful screening campaign against a large small molecule chemical library, but moreover enabled the discovery of several unique classes of molecules with distinct mechanisms of action and selectivity against the related placental (PLAP) and intestinal (IAP) alkaline phosphatase isozymes. This illustrates the underappreciated impact of the underlying fundamental assay configuration on screening success, beyond mere signal generation and detection formats. Full article

In spite of significant progress in anti-HIV-1 therapy, current antiviral chemo-therapy still suffers from deleterious side effects and emerging drug resistance. Therefore, the development of novel antiviral drugs remains a crucial issue for the fight against AIDS. HIV-1 integrase is a key enzyme in the replication cycle of the retrovirus since it catalyzes the integration of the reverse transcribed viral DNA into the chromosomal DNA. Efforts to develop anti-integrase drugs started during the early nineties, culminating with the recent approval of Raltegravir. The discovery and the development of the styrylquinoline inhibitor class was an important step in the overall process. In this review we have described the key synthetic issues and the structure-activity relationship of this family of integrase inhibitors. Crystallographic and docking studies that shed light on their mechanism of action are also examined. Full article

Artemisia annua is currently the only commercial source of the sesquiterpene lactone artemisinin.Since artemisinin was discovered as the active component of A. annua in early 1970s, hundreds of papers have focused on the anti-parasitic effects of artemisinin and its semi-synthetic analogs dihydroartemisinin, artemether, arteether, and artesunate. Artemisinin per se has not been used in mainstream clinical practice due to its poor bioavailability when compared to its analogs. In the past decade, the work with artemisinin-based compounds has expanded to their anti-cancer properties. Although artemisinin is a major bioactive component present in the traditional Chinese herbal preparations (tea), leaf flavonoids, also present in the tea, have shown a variety of biological activities and may synergize the effects of artemisinin against malaria and cancer. However, only a few studies have focused on the potential synergistic effects between flavonoids and artemisinin. The resurgent idea that multi-component drug therapy might be better than monotherapy is illustrated by the recent resolution of the World Health Organization to support artemisinin-based combination therapies (ACT), instead of the previously used monotherapy with artemisinins. In this critical review we will discuss the possibility that artemisinin and its semi-synthetic analogs might become more effective to treat parasitic diseases (such as malaria) and cancer if simultaneously delivered with flavonoids. The flavonoids present in A. annua leaves have been linked to suppression of CYP450 enzymes responsible for altering the absorption and metabolism of artemisinin in the body, but also have been linked to a beneficial immunomodulatory activity in subjects afflicted with parasitic and chronic diseases. Full article

The chemistry and biochemistry of the vitamin B₁₂ compounds (cobalamins, XCbl) are described, with particular emphasis on their structural aspects and their relationships with properties and function. A brief history of B₁₂, reveals how much the effort of chemists, biochemists and crystallographers have contributed in the past to understand the basic properties of this very complex vitamin. The properties of the two cobalamins, the two important B₁₂ cofactors Ado- and MeCbl are described, with particular emphasis on how the Co-C bond cleavage is involved in the enzymatic mechanisms. The main structural features of cobalamins are described, with particular reference to the axial fragment. The structure/property relationships in cobalamins are summarized. The recent studies on base-off/base-on equilibrium are emphasized for their relevance to the mode of binding of the cofactor to the protein scaffold. The absorption, transport and cellular uptake of cobalamins and the structure of the B₁₂ transport proteins, IF and TC, in mammals are reviewed. The B₁₂ transport in bacteria and the structure of the so far determined proteins are briefly described. The currently accepted mechanisms for the catalytic cycles of the AdoCbl and MeCbl enzymes are reported. The structure and function of B₁₂ enzymes, particularly the important mammalian enzymes methyltransferase (MetH) and methyl-malonyl-coenzymeA mutase (MMCM), are described and briefly discussed. Since fast proliferating cells require higher amount of vitamin B₁₂ than that required by normal cells, the study of B₁₂ conjugates as targeting agents has recently gained importance. Bioconjugates have been studied as potential agents for delivering radioisotopes and NMR probes or as various cytotoxic agents towards cancer cells in humans and the most recent studies are described. Specifically, functionalized bioconjugates are used as “Trojan horses” to carry into the cell the appropriate antitumour or diagnostic label. Possible future developments of B₁₂ work are summarized. Full article

Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate the optimization of leads into drug candidates. The quantitative structure–activity relationship (QSAR) formalisms are among the most important strategies that can be applied for the successful design new molecules. This review provides a comprehensive review on the evolution and current status of 4D-QSAR, highlighting present challenges and new opportunities in drug design. Full article

The synthetic potential of stereoselective, palladium-catalyzed hydro(het)arylation reactions of bi-, tri- and tetracyclic (hetero)alkenes in the presence of phospines and arsines as highly efficient ligands was studied. The mechanism of this reductive Heck reaction becomes more complex in the case of benzonorbornenes. Hydroarylation of diazabicyclo-[2.2.1]heptenes provides a stereoselective access to aryldiaminocyclopentanes. Electron-deficient arylpalladium complexes shift the reaction towards the product of a formal 1,2-hydrazidoarylation reaction of 1,3-cyclopentadiene by a stereoselective C-N cleavage. Due to steric reasons, rigid bicyclo[2.2.2]octenes react slower in hydroarylation reactions than the corresponding bicyclo[2.2.1]heptenes. The more flexible bicyclo[4.2.2]decene system already tends to undergo domino-Heck reactions, even under reductive conditions. When a tetracyclic cis-allylcyclopropane is carbopalladated in the presence of formates, the neighboring cyclopropane ring is attacked in the first reported example of a π,σ domino-Heck reaction. Full article

This paper provides a brief review of recent progress in the field of metal coordination polymers assembled from azole-containing carboxylic acids and gives a diagrammatic summary of the diversity of topological structures in the resulting infinite metal-organic coordination networks (MOCNs). Azole-containing carboxylic acids are a favorable kind of multifunctional ligand to construct various metal complexes with isolated complexes and one, two and three dimensional structures, whose isolated complexes are not the focus of this review. An insight into the topology patterns of the infinite coordination polymers is provided. Analyzed topologies are compared with documented topologies and catalogued by the nature of nodes and connectivity pattern. New topologies which are not available from current topology databases are described and demonstrated graphically. Full article

Plant secondary metabolites include an array of bioactive constituents form both medicinal and food plants able to improve human health. The exposure to these phytochemicals, including phenylpropanoids, isoprenoids and alkaloids, through correct dietary habits, may promote health benefits, protecting against the chronic degenerative disorders mainly seen in Western industrialized countries, such as cancer, cardiovascular and neurodegenerative diseases. In this review, we briefly deal with some plant foods and herbs of traditional medicines and diets, focusing on their neuroprotective active components. Because oxidative stress and neuroinflammation resulting from neuroglial activation, at the level of neurons, microglial cells and astrocytes, are key factors in the etiopathogenesis of both neurodegenerative and neurological diseases, emphasis will be placed on the antioxidant and anti-inflammatory activity exerted by specific molecules present in food plants or in remedies prescribed by herbal medicines. Full article

The number of synthetic methods enabling the preparation of ammonium-based rotaxanes has increased very rapidly in the past ten years. The challenge in the synthesis of rotaxanes results from the rather weak interactions between the ammonium-containing rod and the crown ether macrocycle in the pseudorotaxane structure that rely mostly on O•H hydrogen bonds. Indeed, no strong base or polar solvent that could break up H-bonding can be used during the formation of rotaxanes because the two components will separate as two distinct entities. Moreover, most of the reactions have to be performed at room temperature to favor the formation of pseudorotaxane in solution. These non-trivial prerequisites have been taken into account to develop efficient reaction conditions for the preparation of rotaxanes and those are described in detail along this review. Full article

Tetrazoles remain a challenge to photochemists. Photolysis leads to cleavage of the tetrazolyl ring, may involve various photodegradation pathways and may produce a diversity of photoproducts, depending on the structure and conformational flexibility of the substituents and the possibility of tautomerism. If the photochemistry of tetrazoles is considered within the frame of synthetic applications the subject is even more challenging, since the ultimate goal is to achieve selectivity and high yield. In addition, the photoproducts must remain stable and allow isolation or trapping, in order to be used in other reactions. This review summarises the photochemical transformations of tetrazole derivatives that can be used as effective synthetic routes to other compounds. Full article