ALBERT

Description: Phytochemical investigation of the seeds of Alpinia katsumadai (Zingiberaceae) led to the isolation and identification of six new diarylheptanoid derivatives, katsumains D–G ( 1 – 4 ), 3-(acetyloxy)-alpinikatin ( 5 ), and 5-(acetyloxy)alpinikatin ( 6 ). The structures of 1 – 6 were elucidated by spectroscopic data analysis including 1D- and 2D-NMR experiments.

Description: The object of this study is the interaction of the cyclic anhydride 2 of (18 α ,19 β )-19-hydroxy-2,3-secooleanane-2,3,28-trioic acid 28,19-lactone ( 1 ) with primary and secondary amines. It was shown that the products of steric control (the corresponding 2-amino-2-oxo-3-oic acids=2-amides) were formed solely upon the opening of the anhydride cycle by secondary amines ( Scheme 2 ), whereas the interaction with primary amines yielded a mixture of isomeric amides ( Scheme 10 ). In the latter case, the solvent provided a noticeable effect on the reaction selectivity, which was demonstrated in the case of 4-methoxybenzylamine. The interaction between the resulting 3-amides and oxalyl chloride yielded the corresponding cyclic imides, whereas under these conditions, 2-amides formed spiropyrrolidinetriones ( Scheme 4 ).

Description: Two novel indole alkaloids with plumeran skeleton, N -benzoyl-12-demethoxycylindrocarine and N -cinnamoyl-12-demethoxycylindrocarine ( 1 and 2 , resp.), were isolated from the MeOH extract of the stem bark of Aspidosperma cylindrocarpon Müll . Arg . These compounds were obtained by high-speed counter-current chromatography, and their structures were elucidated on the basis of their NMR (1D and 2D) data. They were tested in vitro against chloroquine-resistant strains of Plasmodium falciparum , and only 2 showed a weak activity ( IC 50 127.97 ng/ml with respect to the standard drug). Several other known compounds, comprising steroids, flavonoids, the rarely found atraric acid, as well as the previously reported alkaloid 3 , were also isolated by conventional chromatographic techniques.

Description: Two new spirostanol saponins, namely elephanosides G and H ( 1 and 2 , resp.) were isolated from the leaves of Yucca elephantipes (Agavaceae), together with the two known furostanol saponins 3 and 4 and the six known flavonoid O - and C -glycosides 5 – 10 . The new structures were elucidated as (3 β ,25 S )-spirost-5-en-3-yl O - β - D -glucopyranosyl-(1→3)- O - β - D -glucopyranosyl-(1→4)- β - D -galactopyranoside ( 1 ) and (3 β ,5 β ,25 R )-3-[(2- O - β - D -glucopyranosyl- β - D -galactopyranosyl)oxy]spirostan-12-one ( 2 ) on the basis of detailed spectroscopic analysis and acidic hydrolysis.

Description: The chemoselectivity in the reaction of 2-diazo-3-oxo-3-phenylpropanal ( 1 ) with aldehydes and ketones in the presence of Et 3 N was investigated. The results indicate that 1 reacts with aromatic aldehydes with weak electron-donating substituents and cyclic ketones under formation of 6-phenyl-4 H -1,3-dioxin-4-one derivatives. However, it reacts with aromatic aldehydes with electron-withdrawing substituents to yield 1,3-diaryl-3-hydroxypropan-1-ones, accompanied by chalcone derivatives in some cases. It did not react with linear ketones, aliphatic aldehydes, and aromatic aldehydes with strong electron-donating substituents. A mechanism for the formation of 1,3-diaryl-3-hydroxypropan-1-ones and chalcone derivatives is proposed. We also tried to react 1 with other unsaturated compounds, including various olefins and nitriles, and cumulated unsaturated compounds, such as N , N′ -dialkylcarbodiimines, phenyl isocyanate, isothiocyanate, and CS 2 . Only with N , N′ -dialkylcarbodiimines, the expected cycloaddition took place.

Description: When treated with LiN i Pr 2 (LDA) at −78°, 1-[(methylsulfanyl)methyl]-2-[(1 Z ,3 E )-4-phenylbuta-1,3-dien-1-yl]benzene easily cyclized to form benzocycloheptenyl anion, which successively underwent intramolecular nucleophilic substitution to give a cyclopropanaphthalene. Similar LDA-mediated cyclization also occurred for 4-phenyl- or 4-methyl-substituted 1-[2-(methoxymethyl)phenyl]buta-1,3-dienes to furnish the corresponding benzocycloheptenes and cyclopropanaphthalenes. A 4- tert -butyl analog also underwent LDA-mediated cyclization to give a benzocycloheptene, but not a cyclopropanaphthalene.

Description: Three new isomeric biisoflavonoids, dapholidins A–C ( 1 – 3 , resp.), have been isolated from the AcOEt-soluble fraction of the MeOH-soluble extract of the roots of Daphne oleoides , along with the known compounds daphwazirin ( 4 ), daphnetin 8- O - β - D -glucopyranoside ( 5 ), daphnin ( 6 ), daphneticin 4″- O - β - D -glucopyranoside ( 7 ), and 6,7-dihydroxy-3-methoxy-8-[2-oxo-2 H -1-benzopyran-7-( O - β - D -glucopyranosyl)-8-yl]-2 H -1-benzopyran-2-one ( 8 ). The structures of the new compounds were determined by spectroscopic analyses, including 1D- and 2D-NMR.

Description: Two spiroheterocyclic 2 H -azirin-3-amines, 1f and 1g , were shown to be useful synthons for the dipeptides N -(4-aminotetrahydro-2 H -pyran-4-yl)prolinate (Thp-Pro) and the corresponding thiopyran derivative, Tht-Pro, respectively. By coupling of 4-bromobenzoic acid with 1f or 1g and saponification, followed by repeating the coupling and saponification steps, oligopeptides of type 4-BrBz-(Thp-Pro) n -OMe and 4-BrBz-(Tht-Pro) n -OMe were prepared, and their conformations were evaluated in solution by NMR techniques and in the crystalline state by X-ray crystallography. All of these sterically highly congested oligopeptides adopt fairly rigid helical conformations. It is interesting to note that the hexapeptide with Thp forms a 3 10 -helix, whereas the Tht analog has a β -bend ribbon spiral confirmation.

Description: Two new naphthoquinones, (2 R )-6,8-dihydroxy- α -dunnione ( 1 ), 6,8-dihydroxy-2,7-dimethoxy-3-(1,1-dimethylprop-2-enyl)-1,4-naphthoquinone ( 2 ), together with three known compounds, (2 R )-6,8-dihydroxy-7-methoxy- α -dunnione ( 3 ), nevadensin ( 4 ), and lysioside C ( 5 ), were isolated from the whole plant of Lysionotus pauciflorus. Their structures were established by spectroscopic methods. Hydroxylated naphthoquinones are reported to occur in a Lysionotus species for the first time. The cytotoxic activities of compounds 1 – 3 were evaluated in vitro against a panel of tumor cell lines.

Description: The three-component reaction of aniline, benzaldehyde, and dienophiles such as 2,3-dihydrofuran, ethyl vinyl ether, 2,3-dihydropyran, and cyclopentadiene can be promoted by ionic liquids like imidazolium salts and guanidinium salts under thermal as well as microwave conditions. The chemical yield as well as the diastereoselectivity of the Povarov reaction strongly depend on the ionic liquid employed. The guanidinium salts can be recycled and reused several times without loss of reactivity.

Description: One new triterpenoid, (3 β ,11 α ,19 β )-3-(butanoyloxy)-11-hydroxytaraxast-20(30)-ene-23,28-dioic acid (clerodendrumic acid; 1 ) was isolated from the hexane extract of the leaves of Clerodendrum glabrum var. glabrum along with heptadecanoic acid ( 2 ). The structure of the new compound was elucidated by interpretation of its NMR (1D and 2D), MS, and IR data. Combined fractions C and D from the column chromatography of the hexane extract exhibited significant antifungal activities (average MIC of 0.10 mg/ml) against Candida albicans and Cryptococcus neoformans. C. albicans was relatively resistant to clerodendrumic acid ( 1 ; MIC 125 μg/ml) and was resistant to heptadecanoic acid ( 2 ; MIC 188 μg/ml). Both compounds had low antibacterial activities against two Gram -positive and two Gram -negative bacteria with average MIC values of 157 and 172 μg/ml, respectively. Compounds 1 and 2 were relatively nontoxic against monkey kidney Vero cells in vitro with IC 50 values of 202.6 and 108.4 μg/ml, respectively.

Description: ABSTRACT Environmental particles are believed to provoke airway inflammation in susceptible individuals by stimulating epithelial cells to release mediators that exacerbate lung diseases. Here, we sought to identify genes expressed throughout the genome by epithelial cells stimulated with TiO 2 particles. A human bronchial epithelial cell line, BEAS-2B, was stimulated with or without 40 µg TiO 2 for 2 h. RNA was purified from cells and subjected to microarray analysis. Genes exhibiting more than a twofold change in RNA expression were selected. Candidate genes were then analyzed using bioinformatics tools, including pathway, ontology, and network analyses. ITGAV mRNA expression levels were measured in BEAS-2B cells using real-time polymerase chain reaction. Among 37,803 genes, 92 genes displayed more than a twofold change in mRNA levels according to the microarray analysis; 87 genes were upregulated while five genes were downregulated. The 92 genes were classified based on functional annotation using a protein information resource database search for biological processes and a pathway search using the KEGG pathway database. These genes are related to macromolecule biosynthesis, metabolic processes and, in particular, RNA metabolism. When genes with more than a threefold change were analyzed, KIF11, ITGAV, SEMA3C, IBTK, and DEK were selected as candidate genes induced by TiO 2 -stimulated BEAS-2B cells. To validate these results, BEAS-2B cells stimulated with 40 µg TiO 2 expressed threefold higher ITGAV mRNA levels compared to those without TiO 2 particle stimulation. We conclude that KIF11, ITGAV, SEMA3C, IBTK, and DEK are candidate genes expressed by epithelial cells when stimulated with TiO 2 particles. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4-methylquinoline, 4-nitroquinoline-1-oxide (4-NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4-methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C-5 to C-8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C-2: phenyl and 3,4-methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C-2 substitution with α-, β-, or γ-pyridinyl groups removed 4-methylquinoline genotoxicity. On the other hand, 4-NQO derivatives whose genotoxic mechanism involves reduction of the C-4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C-2 of 4-NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure–genotoxicity relationships and bioassay-guided quinoline synthesis. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT In the past few decades, there has been much concern about the adverse health effects of environmental contaminants in general and Crude Oil in particular around the Niger Delta region of Nigeria where all the crude Oil exploration is taking place. Studies have shown the repro-toxic effects of Bonny-light crude oil (BLCO). However, the insight into the mechanisms of gonadal toxicity induced by BLCO is not well known. In this study, we sought to elucidate the mechanism(s) underpinning the gonadal effects within hours of exposure to BLCO. Experimental rats were divided into five groups of four each. Animals were orally administered with a single dose of BLCO (800 mg/kg body weight) and killed at 0, 6, 12, 24, and 72 h post-treatment. The levels and time-course of induction of stress response proteins and apoptosis-related proteins like cytochorome C, caspase 3 and procaspase 9, Fas–FasL, NF-kB and TNF-α were determined to assess sequential induction of apoptosis in the rat testis. DNA damage was assessed by TUNEL assay. Administration of BLCO resulted in a significant increase in the levels of stress response proteins and apoptotis- related proteins as early as 6 h following exposure. Time-dependent elevations in the levels of the proteins were observed. The DNA damage was measured and showed time-dependent increase in the TUNEL positive cells of testicular cells. The study demonstrates induction of testicular apoptosis in adult rats following exposure to a single dose of BLCO. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Divalent lead (Pb 2+ ) is a common industrial pollutant epidemiologically associated with gastric cancers. Pb 2+ was found to promote tumorigenesis, which may include interleukin (IL)-8, a pro-inflammatory chemokine that promotes angiogenesis and tumor metastasis. Given that the gastrointestinal tract is a major route of Pb 2+ exposure, we investigated the ability of Pb 2+ to induce IL-8 expression in gastric carcinoma cells and its underlying mechanism. At a concentration of 0.1 μM, Pb 2+ induced IL-8 gene activation in gastric carcinoma AGS cells. Using a IL-8 promoter-deletion analysis, transcription factor activator protein 1 (AP-1) was identified as a necessary component of Pb 2+ -induced IL-8 gene activation. Upregulation of the IL-8 gene was abrogated by the MEK inhibitor, PD98059, and partially suppressed by the epidermal growth factor receptor inhibitors, AG1478 and PD153035. Furthermore, c-Jun protein expression was induced in cells treated with Pb 2+ , and overexpression of c-Jun enhanced Pb 2+ -induced IL-8 activation. Collectively, our findings highlight the pivotal roles of AP-1 and extracellular signal-regulated kinase in signal transduction of Pb 2+ -induced IL-8 gene activation. These molecules may be potential therapeutic targets for Pb 2+ -related inflammation leading to stomach carcinogenesis. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Beginning early in the 19th century, developments in crystallography, optics, and chemistry in France set the stage for the discovery of molecular chirality by Louis Pasteur in 1848. He found that the crystallization of the sodium ammonium salt of ‘ paratartaric acid ’, a mysterious ‘ isomer ’ of natural (+)-tartaric acid (TA), produced two different crystal types that were non-superimposable mirror-image forms of each other. He separated the two types and found their optical rotations in solution opposite in direction and equal in absolute magnitude. This led him to conclude that paratartaric acid is a combination of two mirror-image molecule types of TA that are ‘ dissymmetric ’, an existing term he adapted to the connotation of today's ‘ chiral ’. In 1857, he found that the two enantiomers of TA were metabolized by a microorganism at drastically different rates, and thereby discovered biological enantioselectivity. In 1886, Italian chemist Arnaldo Piutti discovered D -asparagine and found that it tasted intensely sweet, in contrast to the known L -asparagine which had no taste. This was the discovery of stereoselectivity at biological receptors. As a result of advances in stereoselective synthesis and enantioselective chromatography during the last decades of the 20th century, in the 1990s the importance of molecular chirality in drug action and disposition began to receive serious attention from drug-regulatory authorities and the pharmaceutical industry, the overall result of which has been the near-complete disappearance of racemic drugs as newly introduced pharmaceuticals.

Description: ABSTRACT In this study, we have evaluated the pulmonary toxicity of MgO nanoparticles (MgO NPs) in rats following their exposure. NPs in phosphate buffered saline + 1% Tween 80 were exposed via intratracheal instillation at a doses of 1 mg/kg or 5 mg/kg into rat lungs and evaluated for various tissue damage markers like alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid and histopathology of lungs at 1, 7, and 30 days of post-exposure intervals. A dose-dependant increase in ALP and LDH activity was observed in BAL fluids of rat lungs than sham control at all post-exposure periods ( P 〈0.05), and a dose-dependant infiltration of interstitial lymphocytes, peribronchiolar lymphocytic infiltration, and dilated and/or congested vessels at 1 day post-exposure period, worsened at 1 week period, and were reduced at 1 month at histology, indicating the pulmonary toxicity of MgO NPs. In conclusion, MgO NPs exposure produced a dose-dependent pulmonary toxicity in rats and was comparable with that of Quartz particles. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: The four new cerebrosides 1 – 4 possessing a unique C 18 9-methylsphinga-4,8-dienine-related moiety and a cyclic octapeptide, 5 , possessing alternating proline and glycine moietes were isolated from the Tuber indicum fermentation mycelium. Their structures were established on the basis of a spectroscopic analysis including NMR and HR-ESI-MS, as well as an acidic methanolysis experiment. To the best of our knowledge, the cerebrosides identified in the present study are quite different from those isolated from Tuber indicum fruiting bodies. Additionally, it was the first time that a cyclic peptide was isolated from the Tuber genus.

Description: Three fluorescent turn-on probes containing 3,6-dichloro-9 H -carbazole as carbazyl part have been designed and synthesized. Among studied anions F − , AcO − , H 2 PO , Cl − , Br − and I − , AcO − showed the strongest binding ability with all probes. The strong basic anions, such as AcO − , H 2 PO , and F − , induced a significant red-shift in absorption and a concomitant increase in fluorescent emission of the probes caused by photoinduced electron transfer (PET). The determination limit of probe 3 ( Scheme 1 ) toward AcO − is 3.0×10 −7   M . 1 H-NMR Titration experiments shed light on the nature of the interaction between the probes and the anions. Theoretical investigation further illustrated the possible binding mode in these host guest interactions and the roles of molecular frontier orbitals in molecular interplay.

Description: This Part 4 continues a general presentation of the principles of stereochemistry with special reference to medicinal compounds and their interactions with biological systems. Here, we discuss and illustrate two major aspects of conformational isomerism, namely a ) the concept of torsional isomerism about single bonds, and b ) the intertwined conformational and configurational aspects of the stereochemistry of cyclic systems. The review begins with a brief reminder of the history and thermodynamics of conformational isomerism, and goes on to explain and illustrate the conventions and graphical representations used for conformers. Examples are then examined, beginning with ethane, the simplest one, and building up to more complex cases, documenting the attractive or repulsive role of substituents. A similar approach is applied when dealing with cyclic systems, although here the presentation necessarily takes into account configurational aspects specific to cyclic systems. The pharmacological implications of the concepts discussed here will be presented in Part 6.

Description: A new eremophilane sesquiterpene, (2 β )-2-deoxo-2-methoxytessaric acid ( 1 ), and two new eudesmane sesquiterpenes, (3 β ,10 α )-3-methoxyleudesma-4,11(13)-dien-12-oic acid ( 2 ) and (3 α ,4 β ,8 α )-4-(acetyloxy)-3-(2,3-dihydroxy)-2-methyl-1-oxobutoxy-8-hydroxyeudesm-7(11)-eno-12,8-lactone ( 3 ), along with the ten known compounds 4 – 13 were isolated from the aerial parts of Laggera pterodonta. The structures of the new compounds were elucidated by spectroscopic analyses, including 2D-NMR data.

Description: A simple synthesis of 2-hydrazinylidene-3-hydroxy-4 H -furo[3,2- c ]pyran-4-ones is described. A mixture of (isocyanoimino)(triphenyl)phosphorane, an aromatic aldehyde, and dehydroacetic acid (=3-acetyl-2-hydroxy-6-methyl-4 H -pyran-4-one) undergo a 1 : 1 : 1 addition reaction under mild conditions to afford the title compounds in excellent yields.

Description: A linear synthesis of the major oxepane fragment of zoapatanol, showing the induction of uterine contractions, and cervical dilation and uterine bleeding (by the concentrated zoapatle tea) in early human pregnancy, isolated from the leaves of Mexican zoapatle plant Montanoa tomentosa , is described from known intermediate involving Sharpless asymmetric epoxidation, bis-epoxide opening reaction with Corey Chaykovsky reagent, ring-closing metathesis reaction, and Horner Wadsworth Emmons olefination reaction as key steps.

Description: Total synthesis of biologically interesting natural and unnatural pyranoflavones has been accomplished starting from readily available 2,4-dihydroxyacetophenone or 2,4-dihydroxy-6-methoxyacetophenone in three steps, i.e. , benzopyran formation, condensation, and cyclization reaction.

Description: On treatment of 3-amino-5-aryl-1 H -pyrazoles 1 with dialkyl dicyanofumarates (=( E )-but-2-enedioates) 4 in boiling 1,2-dichloroethane, two competitive reactions occurred leading to 3-aryl-5-cyano-6,7-dihydro-6-oxo-1 H -pyrazolo[3,4- b ]pyridine-4-carboxylates 10 and 7-amino-2-arylpyrazolo[1,5- a ]pyrimidine-5,6-dicarboxylates 11 . In DMF at room temperature, as well as at 100°, only compounds 10 were isolated. The formation of the major products of type 10 was rationalized via Michael addition of 1 as a C ( 4 )-nucleophile onto 4 , followed by HCN elimination and lactamization. On the other hand, the minor products 11 result from a Michael addition of 1 onto 4 via the NH 2 group, and subsequent HCN elimination and cyclization. The structures of the products have been established by X-ray crystallography.

Description: A phytochemical investigation of the MeOH extract of Valeriana fauriei Briq . roots resulted in the isolation of two new sesquiterpenes, isovalerianin A (=(1 β ,4 Z ,6 β ,8 α )-8-(acetyloxy)-1,10-dihydroxy-6,11-cyclogermacr-4-en-15-al= rel -(1 R ,2 Z ,6 S ,7 R ,9 R ,10 S )-9-(acetyloxy)-6,7-dihydroxy-7,11,11-trimethylbicyclo[8.1.0]undec-2-ene-3-carboxaldehyde; 1 ) and valerianin C (=(2 α ,3 α ,6 α ,8 α )-3-(acetyloxy)-2,4,8-trihydroxyguai-1(10)-ene-12,6-lactone= rel -(3 R ,3a S ,4 R ,7 S ,8 S ,9 R ,9a R ,9b R )-8-(acetyloxy)-3a,4,5,7,8,9,9a,9b- octahydro-4,7,9-trihydroxy-3,6,9-trimethylazuleno[4,5- b ]furan-2(3 H )-one; 2 ), together with six known compounds, i.e. , camphor, methyl 4-hydroxybenzoate, 2-methoxybenzoic acid, benzoic acid, quercetin, and kaempferol. The structures of the compounds were established by detailed spectral analysis and comparison with previously reported data.

Description: To investigate the effects of ellagic acid on the growth inhibition of TSGH8301 human bladder cancer cells in vitro , cells were incubated with various doses of ellagic acid for different time periods. The phase-contrast microscope was used for examining and photographing the morphological changes in TSGH8301 cells. Flow cytometric assay was used to measure the percentage of viable cells, cell cycle distribution, apoptotic cells, ROS, mitochondrial membrane potential (Δ Ψm ), Ca 2+ , caspase-9 and -3 activities in TSGH8301 cells after exposure to ellagic acid. Western blotting was used to examine the changes of cell cycle and apoptosis associated proteins levels. Results indicated that ellagic acid induced morphological changes, decreased the percentage of viable cells through the induction of G0/G1 phase arrest and apoptosis, and also showed that ellagic acid promoted ROS and Ca 2+ productions and decreased the level of Δ Ψm and promoted activities of caspase-9 and -3. The induction of apoptosis also confirmed by annexin V staining, comet assay, DAPI staining and DNA gel electrophoresis showed that ellagic acid induced apoptosis and DNA damage in TSGH8301 cells. Western blotting assay showed that ellagic acid promoted p21, p53 and decreased CDC2 and WEE1 for leading to G0/G1 phase arrest and promoting BAD expression, AIF and Endo G, cytochrome c , caspase-9 and -3 for leading to apoptosis in TSGH8301 cells. On the basis of these observations, we suggest that ellagic acid induced cytotoxic effects for causing a decrease in the percentage of viable cells via G0/G1 phase arrest and induction of apoptosis in TSGH8301 cells. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: 2,3-Dihydro-4 H -thiopyrano[2,3- b ]pyridin-4-ones 4 were prepared by a three-step sequence from commercially available 2-chloropyridine ( 1 ). Thus, successive treatment of 1 with i Pr 2 NLi (LDA) and α , β -unsaturated aldehydes gave 1-(2-chloropyridin-3-yl)alk-2-en-1-ols 2 , which were oxidized with MnO 2 to 1-(2-chloropyridin-3-yl)alk-2-en-1-ones 3 . The reactions of 3 with NaSH⋅ n H 2 O proceeded smoothly at 0° in DMF to provide the desired thiopyranopyridinones. Similarly, 2,3-dihydro-4 H -thiopyrano[2,3- c ]pyridin-4-ones 8 and 2,3-dihydro-4 H -thiopyrano[3,2- c ]pyridin-4-ones 12 were obtained starting from 3-chloropyridine ( 5 ) and 4-chloropyridine ( 9 ), respectively.

Description: Three new ent -kaurane diterpenoids, (4 α )-19-nor- ent -kaurane-4,16,17-triol ( 1 ), (4 α ,16 α )-17-(acetyloxy)-19-nor- ent -kaurane-4,16 - diol ( 2 ), and 17-hydroxy- ent -kaur-15-en-19-al ( 3 ), together with 11 known compounds, were isolated from the stem bark of Annona squamosa L. The structures of 1 – 3 were identified by analysis of their spectroscopic data. All compounds were evaluated for cytotoxic activity against human lung cancer (95-D) and ovarian cancer (A2780) cell lines, and compounds 3, 5, 7, 11 – 14 exhibited promising antiproliferative activities with IC 50 values ranging from 0.38 to 34.66 μ M .

Description: Two new triazoles, chrysotriazoles A and B ( 1 and 2 , resp.), along with two known quinazolinones, 3 and 4 , two known 2-(4-hydroxyphenyl)acetamides, 5 and 6 , and two known N -(4-hydroxystyryl)formamides, 7 and 8 , were isolated and identified from the culture extract of Penicillium chrysogenum EN-118, an endophytic fungus obtained from the marine brown alga Sargassum pallidium. The structures of the isolated compounds were elucidated by NMR-spectroscopic analysis, and that of compound 1 was confirmed by X-ray crystallographic analysis of its p -bromobenzoate derivative. Compounds 4, 5 , and 7 showed moderate cytotoxicities against Du145, A-549, and HeLa cell lines.

Description: The reaction of N , N -bis(diphenylphosphino)naphthalen-1-amine ( 1 ) with [M(CO) 6 ] (M=Cr, Mo, W; 1 : 1 molar ratio) afforded cis -[M(CO) 4 ( 1 )] 2 (M=Cr), 3 (M=Mo), and 4 (M=W). Compounds 2 – 4 were identified and characterized by elemental analysis and multinuclear NMR ( 1 H-, 13 C-, and 31 P-NMR) and IR spectroscopy. A crystal-structure determination of complex 3 was carried out.

Description: Phytochemical investigation of the whole herbs of Aconitum tanguticum ( Maxim .) Stapf var. trichocarpum Hand.-Mazz . led to the isolation of one heteratisine-hetidine-type bis-diterpenoid alkaloid, trichocarpidine ( 1 ), three hetidine-hetisine type bis-diterpenoid alkaloids, trichocarpinine A–C ( 2 – 4 , resp.), together with nine known compounds. Their structures were elucidated by spectroscopic analyses.

Description: Four metal-ion-binding nucleosides, viz. 2,6-bis(1-methylhydrazinyl)-9-( β - D -ribofuranosyl)-9 H -purine ( 2a ) and its N -acetylated derivative, 2b , 2,4-bis(3,5-dimethyl - 1 H -pyrazol-1-yl)-5-( β - D -ribofuranosyl)pyrimidine ( 3 ), and 2,4-bis(1-methylhydrazinyl)-5-( β - D -ribofuranosyl)pyrimidine ( 4 ) have been synthesized. The ability of these nucleosides and the previously prepared 2,6-bis(3,5-dimethyl - 1 H -pyrazol-1-yl)-9-( β - D -ribofuranosyl)-9 H -purine to form Pd 2+ - and Hg 2+ -mediated complexes with uridine has been studied by 1 H-NMR spectroscopy. To obtain additional support for the interpretation of the NMR data, comparative measurements on the ternary-complex formation between pyridine-2,6-dicarboxamide ( 5 ), pyrimidine nucleosides, and K 2 PdCl 4 were carried out.

Description: Organotin complexes 1 – 6 of the general formula [SnR 2 L] and [(SnR 3 ) 2 L] (L=phenanthrenequinone dioximato – a bidentate ligand, R=Me, Bu, and Ph) were synthesized by the reaction of the sodium salt of the ligand H 2 L (prepared in situ with MeONa) and SnR 2 Cl 2 /SnR 3 Cl in 1 : 1 and 1 : 2 molar ratios. The physical and spectral properties of the newly synthesized complexes 1 – 6 are described. DFT and HF Calculations were performed to confirm the proposed structures.

Description: The 3-allyl-2-methylquinazolin-4(3 H )-one ( 1 ), a model functionalized terminal olefin, was submitted to hydroformylation and reductive amination under optimized reaction conditions. The catalytic carbonylation of 1 in the presence of Rh catalysts complexed with phosphorus ligands under different reaction conditions afforded a mixture of 2-methyl-4-oxoquinazoline-3(4 H )-butanal ( 2 ) and α ,2-dimethyl-4-oxoquinazoline-3(4 H )-propanal ( 3 ) as products of ‘linear’ and ‘branched’ hydroformylation, respectively ( Scheme 2 ). The hydroaminomethylation of quinazolinone 1 with arylhydrazine derivatives gave the expected mixture of [(arylhydrazinyl)alkyl]quinazolinones 5 and 6 , besides a small amount of 2 and 3 ( Scheme 3 ). The tandem hydroformylation/reductive amination reaction of 1 with different amines gave the quinazolinone derivatives 7 – 10 . Compound 10 was used to prepare the chalcones 11a and 11b and pyrazoloquinazolinones 12a and 12b ( Scheme 4 ).

Description: ABSTRACT Chemotherapy remains an important approach in the fight against malaria. Artemether–lumefantrine combination is widely in use due to its effectiveness against Plasmodium falciparum . Misuse in the form of multiple repeated doses of this anti-malaria drug is rampant in Nigeria. This study was designed to assess the hepatotoxic and clastogenic potential of extreme misuse of artemether–lumefantrine in rats. Graded doses of artemether–lumefantrine (1–5 mg/kg body weight) were administered by oral gavage for 6 weeks, twice daily, for 3 consecutive days per week. Artemether–lumefantrine, at all doses, did not have significant effects on the body and relative liver weight of treated group compared to the negative control group. The mean γ-glutamyltransferase, alanine, and aspartate aminotransaminase activity in groups of artemether–lumefantrine treated rats were significantly higher ( p 〈 0.05) than that of the negative control group indicating that repeated administration of artemether–lumefantrine may be hepatotoxic. Findings from histological analyses of liver cross-section support the enzyme pattern of hepatoxicity. In addition, the drug, at all experimental doses, significantly induced ( p 〈 0.05) formation of micronucleated polychromatic erythrocytes in the bone marrow cells of the treated rats compared with the negative control indicating clastogenic potential of the drug when misused. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Tattoo belongs to the group of carbamate fungicides and contains Mancozeb (ethylene(bis)dithiocarbamate) as its main constituent. The toxicity of Mancozeb to living organisms, particularly fish, is not resolved. This work investigated the effects of 96 h of exposure to 3, 5, or 10 mg L −1 of Tattoo (corresponding to 0.9, 1.5, or 3 mg L −1 of Mancozeb) on the levels of oxidative stress markers and the antioxidant enzyme system of brain, liver, and kidney of goldfish, Carassius auratus ). In liver, Tattoo exposure resulted in increased activities of superoxide dismutase (SOD) by 70%–79%, catalase by 23%–52% and glutathione peroxidase (GPx) by 49%. The content of protein carbonyls (CP) in liver was also enhanced by 92%–125% indicating extensive damage to proteins. Similar increases in CP levels (by 98%–111%) accompanied by reduced glucose-6-phosphate dehydrogenase activity (by 13%–15%) was observed in kidney of fish exposed to Tattoo; however, SOD activity increased by 37% in this tissue after treatment with 10 mg L −1 Tattoo. In brain, a rise in lipid peroxide level (by 29%) took place after exposure to 10 mg L −1 Tattoo and was accompanied by elevation of high-molecular mass thiols (by 14%). Tattoo exposure also resulted in a concentration-dependent decrease in glutathione reductase activity (by 26%–37%) in brain. The data collectively show that exposure of goldfish to 3–10 mg L −1 of the carbamate fungicide Tattoo resulted in the development of mild oxidative stress and activation of antioxidant defense systems in goldfish tissues. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Ecotoxicological studies that focus on a single endpoint might not accurately and completely represent the true ecological effects of a contaminant. Exposure to atrazine, a widely used herbicide, disrupts endocrine function and sexual development in amphibians, but studies involving live-bearing reptiles are lacking. This study tracks several effects of atrazine ingestion from female Northern Watersnakes ( Nerodia sipedon ) to their offspring exposed in utero . Twenty-five gravid N. sipedon were fed fish dosed with one of the four levels of atrazine (0, 2, 20, or 200 ppb) twice weekly for the entirety of their gestation period. Endpoints for the mothers included blood estradiol levels measured weekly and survival more than 3 months. Endpoints for the offspring included morphometrics, clutch sex ratio, stillbirth, and asymmetry of dorsal scales and jaw length. Through these multiple endpoints, we show that atrazine ingestion can disrupt estradiol production in mothers, increase the likelihood of mortality from infection, alter clutch sex ratio, cause a higher proportion of stillborn offspring, and affect scale symmetry. We emphasize the need for additional research involving other reptile species using multiple endpoints to determine the full range of impacts of contaminant exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Microcystin-LR (MC-LR) is a potent inhibitor of protein phosphatases 1 and 2A, and has potent hepatotoxicity and tumor promotion activity. Numerous studies on MC-LR toxicity have been conducted in rat hepatocytes, but few studies of the effects of microcystins on human hepatocytes have been done. In this study, HL7702 cells (a human normal liver cell line) were incubated in MC-LR for 24 h. The existence of MC-LR in HL7702 cells was confirmed. Furthermore, PP2A activity and the alteration of PP2A subunits were assessed. The results show that PP2A activity decreased from the concentration of 1 μM MC-LR, showing a concentration-dependent decline, to about 34% at 10 μM MC-LR. This activity undergone opposite change with alternations of phosphorylated Y307-PP2A/C and PP2A/C subunit but showed same change with the alteration of the ratio of methylated L309-PP2A/C to PP2A/C. B55α, a regulatory subunit of PP2A, was slightly increases in cells treated with the highest concentration of MC-LR (10 μM), and colocalized increasedly with rearranged-microtubules after 1 μM MC-LR exposure. However, the proportion of early apoptotic cells did not show any change at various concentration of MC-LR for 24 h. To our knowledge, this is the first report showing MC-LR-induced alteration of PP2A phosphatase in human cultured hepatocytes, and the mechanism of action seems to be similar as described before in vitro . The alteration of PP2A and microtubule seems to be the early event induced by MC-LR exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Nonpersistent pesticides are considered less harmful for the environment, but their impact as endocrine disruptors has not been fully explored. The pesticide Switch was applied to grape vines, and the maximum residue concentration of its active ingredients was quantified. The transactivation potential of the pesticides Acorit, Frupica, Steward, Reldan, Switch, Cantus, Teldor, and Scala and their active compounds (hexythiazox, mepanipyrim, indoxacarb, chlorpyrifos-methyl, cyprodinil, fludioxonil, boscalid, fenhexamid, and pyrimethanil) were tested on human estrogen receptor α (ERα), androgen receptor (AR) and arylhydrocarbon receptor (AhR) in vitro . Relative binding affinities of the pure pesticide constituents for AR and their effect on human breast cancer and prostate cancer cell lines were evaluated. Residue concentrations of Switch's ingredients were below maximum residue limits. Fludioxonil and fenhexamid were ERα agonists (EC 50 -values of 3.7 and 9.0 μM, respectively) and had time-dependent effects on endogenous ERα-target gene expression (cyclin D1, progesterone receptor, and nuclear respiratory factor 1) in MCF-7 human breast cancer cells. Fludioxonil, mepanipyrim, cyprodinil, pyrimethanil, and chlorpyrifos-methyl were AhR-agonists (EC 50 s of 0.42, 0.77, 1.4, 4.6, and 5.1 μM, respectively). Weak AR binding was shown for chlorpyrifos-methyl, cyprodinil, fenhexamid, and fludioxonil. Assuming a total uptake which does not take metabolism and clearance rates into account, our in vitro evidence suggests that pesticides could activate pathways affecting hormonal balance, even within permitted limits, thus potentially acting as endocrine disruptors. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: Silver nanoparticles, chemically neutral particles in the size range of 1–100 nm, express strong antimicrobial activity and therefore have a broad range of applications. The increased use of consumer products with nanosilver (nanoAg) may result in its release into the environment, and may particularly affect aquatic systems. The mechanisms of the harmful effects of nanoAg against aquatic organisms are unclear. Therefore, in the present study we investigate the pro-oxidative potential of these nanoparticles in experimentally exposed crayfish Orconectes limosus . Markers of oxidative stress and parameters of the antioxidant cell defense system such as total glutathione, glutathione reductase and the level of sulfhydryl groups were examined in the hepatopancreas of both sexes of O. limosus collected seasonally from Białe Lake (Poland) and subsequently exposed to nanoAg particles for 2 weeks. Exposure to nanoAg led to a high concentration-dependent increase in the rate of lipid peroxidation and a decrease of protein-bound SH groups which indicates protein oxidation. These markers of oxidative stress were accompanied by decreased levels of thiols and reduced activity of glutathione reductase. These results indicate a deficiency of reduced glutathione and suggest that the exposed organisms have less efficient antioxidative mechanisms available to counter ROS-mediated cellular stress. Furthermore, we find that confocal microscopy is of limited utility in monitoring the presence of silver nanoparticles in tissues of exposed crayfish. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: The objective of this research was to investigate the neurotoxic effects of pyrethroid pesticide lambda-cyhalothrin by the modulation of cytochrome P450 with piperonyl butoxide in the brain of juvenile Oreochromis niloticus . The fish were exposed to 0.48 μg L −1 (1/6 of the 96-h LC 50 ) lambda-cyhalothrin and 10 μg L −1 piperonyl butoxide for 96 h and 15 days. tGSH, GSSG, TBARS contents, GPx, GR, GST, and AChE enzymes activities were determined by spectrophotometrical methods and Hsp70 content was analyzed by ELISA technique. Lambda-cyhalothrin had no significant effect on the components of GSH redox system, lipid peroxidation and Hsp70 levels but inhibited AChE activity. In the presence of piperonyl butoxide, lambda-cyhalothrin caused increases in tGSH, GSSG, TBARS and Hsp70 contents, GST activity, and decrease in AChE activity. Present results showed that in the presence of piperonyl butoxide, lambda-cyhalothrin caused neurotoxic effects by increasing oxidative stress. Adaptation to its oxidative stress effects may be supplied by GSH-related antioxidant system. Piperonyl butoxide revealed neurotoxic effect of lambda-cyhalothrin. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: The ability to design properly folded β -peptides with specific biological activities requires detailed insight into the relationship between the amino acid sequence and the secondary and/or tertiary structure of the peptide. One of the most frequently used spectroscopic techniques for resolving the structure of a biomolecule is NMR spectroscopy. Because only signal intensities and frequencies are recorded in the experiment, a conformational interpretation of the recorded data is not straightforward, especially for flexible molecules. The occurrence of conformational and/or time averaging, and the limited amount and accuracy of experimental data hamper the precise conformational determination of a biomolecule. In addition, the relation between experimental observables with the underlying conformational ensemble is often only approximately known, thereby aggravating the difficulty of structure determination of biomolecules. The problematic aspects of structure refinement based on NMR nuclear Overhauser effect (NOE) intensities and 3 J -coupling data are illustrated by simulating a β -octapeptide in explicit MeOH and H 2 O as solvents using three different force fields. NMR Data indicated that this peptide would fold into a 3 14 -helix in MeOH and into a hairpin in H 2 O. Our analysis focused on the conformational space visited by the peptide, on structural properties of the peptide, and on agreement of the MD trajectories with available NMR data. We conclude that 1 ) although the 3 14 -helical structure is present when the peptide is solvated in MeOH, it is not the only relevant conformation, and that 2 ) the NMR data set available for the peptide, when solvated in H 2 O, does not provide sufficient information to derive a single secondary structure, but rather a multitude of folds that fulfill the NOE data set.

Description: Catalytic base-induced decarboxylation of polyunsaturated α -cyano- β -methyl acids derived from malonic acid led to the corresponding nitriles 3 ( Schemes 2 and 3 ), 6 ( Scheme 5 ), and 9 ( Scheme 6 ). This decarboxylation occurred with previous deconjugation of the α , β -alkene moiety of the α -cyano- β -methyl acid, leading to an α -cyano- β -methylene propanoic acid which was easily decarboxylated (see Scheme 2 ). β -Methylene intermediates, in some cases, could be isolated; mechanistic pathways are proposed. The nitriles 3, 6 , and 9 were reduced to the sesquiterpene aldehydes 4 ( β -end group), 7 ( φ -end group), and 10 ( ψ -end group), respectively.

Description: Environmental pollution with synthetic estrogens may pose a serious threat to reproduction of aquatic wildlife species. The current study describes the effects of 17α-ethynylestradiol (EE 2 ) on the structure of the testis in tench ( Tinca tinca ). Adult male tench were exposed to sublethal doses of EE 2 (50, 100, and 500 μg/Kg t.w.) under semistatic conditions for a period of 30 days. The condition factor (CF), testicular somatic index (TSI), and histology (including a morphometric analysis) of the testis were examined. No consistent differences were observed in the CF of EE 2 -exposed tench when compared with nonexposed fish. A significant decrease in TSI could only be observed at a 50 μg/Kg t.w. EE 2 dose (p 〈 0.05) when compared with the control group. The histopathology of the testis was associated with loss of normal tubular structure with increased doses of exposure, decrease of tubule number, degeneration in Sertoli and Leydig cells, increase in necrotic testicular cells including formation of syncytia structures and, finally, a high incidence of fish with early primary oocytes at 100 and 500 μg/Kg t.w. EE 2 . These results indicate that long-term exposure to EE 2 may produce clear negative effects on testicular structure in tench. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: A stereoselective total synthesis of multiplolide A ( 1 ) and of its diastereoisomer 2 was described from easily accessible starting materials ( Schemes 2 – 4 ). The synthetic strategy involves a Jacobsen resolution, Sharpless epoxidation, Swern oxidation, Yamaguchi reaction, and ring-closing metathesis (RCM).

Description: Dehydrohedione (DHH) 1 may be obtained in 20% overall yield by a Reformatsky reaction with enone methyl ether 3b , followed by acidic workup of the crude reaction mixture. Alternatively, epoxidation (3-chloroperbenzoic acid, CH 2 Cl 2 , 84% yield) of the tertiary allyl alcohol derivative 4 affords a 1 : 2 mixture of 8a and 8b . The latter epoxy ester 8b may also be obtained stereoselectively either from 4 ( t BuO 2 H, [Mo(CO) 6 ], 1,2-dichloroethane, 70°, 62% yield; or t BuO 2 H, [VO(acac) 2 ], decane, 20°, 92% yield), or from 5 (AcOMe, LiN(SiMe 3 ) 2 , THF, −78°, 84–87%). BF 3 ⋅Et 2 O-Catalyzed cascade rearrangement and OH elimination of 8a afford selectively DHH 1 in 88% yield. The cis disposition of the side chains of the weakly odoriferous hedione-like analogues 2b and 2c was maintained by means of either an epoxy or a cyclopropane moiety.

Description: A series of β -hydroxynitriles were efficiently synthesized from the regioselective ring opening of oxiranes by cyanide anion in the presence of silica-bound 3-{2-[poly(ethylene glycol)]ethyl}-substituted 1-methyl-1 H -imidazol-3-ium bromide (SiO 2 PEG ImBr) as a novel recoverable phase-transfer catalyst in H 2 O ( Scheme 1 and Table 2 ). The workup procedure was straightforward, and the catalyst could be reused over four times with almost no loss of catalytic activity and selectivity.

Description: 2-(1-Aryl-2-methoxyethenyl)benzaldehydes 2 , obtained by successive treatment of 1-(1-aryl-2-methoxyethenyl)-2-bromobenzenes 1 with BuLi and 1-formylpiperidine, were transformed to the corresponding phenylhydrazones 3 on treatment with PhNHNH 2 . When these hydrazones were allowed to react with conc. HBr, cyclization, followed by dehydrogenation with air occurred, furnished 3-aryl-2-methoxyinden-1-one ( Z )-phenylhydrazones 4 .

Description: Two series of functionalized single and double side-chained lipid molecules ( Schemes 1 and 2 ) were prepared. The compounds carry either terminal COOH, OH, or halogen substituents. Moreover, the double side-chained lipid 18 carries an internal alkyne functionality. The latter compound was used to hydrophobize thymidine at N(3) by base-catalyzed alkylation. Additionally, fully protected thymidine, 32 , was N(3) -alkylated with the double side-chained alcohol 9 applying Mitsunobu reaction conditions.

Description: The first stereoselective total synthesis of the naturally occurring anti-emetic diarylheptanoid (3 R ,5 R )-1-(4-hydroxyphenyl)-7-phenylheptane-3,5-diol ( 1 ) was accomplished starting from 4-hydroxybenzaldehyde and involving a Sharpless kinetic resolution and an asymmetric epoxidation as the key steps ( Scheme 2 ). The enantiomer 1a of this compound was also simultaneously prepared.

Description: A simple, convenient, and efficient method for the formation of functionalized dibenzo[ b , f ]oxepins and their analogs bearing both electron-donating and electron-withdrawing groups has been developed via a one-pot cascade reaction. Most starting materials are commercially available 2-(2-hydroxyphenyl)acetonitriles and 2-haloarylaldehydes. The procedure makes use of Cs 2 CO 3 as the base, and DMF as solvent under copper-assisted/copper-free conditions. The reaction has a comprehensive group tolerance for substrates. Most of the reactions were complete within 1 h in good-to-excellent yields, and the reaction temperatures were relatively low. The protocol could be scaled up to grams without lowering the yield. A reaction mechanism was also proposed.

Description: A new glycine derivative, podocarpiamide ( 1 ), a new indole alkaloid, 1-methoxy-1 H -indol-3-ethanol ( 2 ), together with two known compounds, 1-methoxy-1 H -indole-3-acetic acid ( 3 ) and methyl 1-methoxy-1 H -indole-3-acetate ( 4 ), were isolated from the fermentation broth of the plant endophytic fungus Pestalotiopsis podocarpi. Their structures were elucidated by extensive spectroscopic analysis including 1D- and 2D-NMR (HSQC, HMBC, and COSY) and MS experiments. Compound 1 has an interesting unusual carbamic acid structure.

Description: Two glucose-derived thiourea derivatives, 2a and 2b , were prepared by addition of the corresponding amino sugars to a solution of 4-nitrobenzoyl isothiocyanate ( Scheme 1 ). The thioureas were isolated as colorless solids in good yields and were fully characterized by NMR spectroscopy, optical rotation, elemental analysis, and also by single-crystal X-ray diffraction. Attempts to obtain Cu II and Ni II bis(chelate) complexes with these thioureas failed. However, the C(1)-protected thiourea derivative 2a reacted with orthopalladated acetato-bridged dimers to afford the corresponding monomeric Pd II complexes 3 and 4 ( Scheme 2 ). In these compounds, the thiourea coordinates to the metal as monoanionic O,S chelate ligand, which was confirmed by X-ray crystallography.

Description: Two new abietane-type diterpenoids, named triptobenzene R ( 1 ) and triptobenzene S ( 2 ), together with three known abietane-type diterpenoids, triptophenolide ( 3 ), triptonodiol ( 4 ), and triptonoterpene methyl ether ( 5 ), were isolated from the roots of Tripterygium wilfordii Hook . f. Their structures and relative configurations were established by detailed spectral studies, including 1D- and 2D-NMR (HSQC, HMBC, and NOESY), and HR-ESI-TOF-MS, and by comparison with published data. Their absolute configurations were assigned by the CD technique, applied for the first time to abietane diterpenes from Tripterygium wilfordii. Compound 2 is the first abietane-type norditerpenoid isolated from the genus Tripterygium.

Description: Four compounds with similar structures and UV spectra were isolated from the fermentation broth of Armillaria mellea by means of preparative HPLC. Their structures were established as methyl (2 S )-1-[2-(furan-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carboxylate ( 1 ), (2 S )-1-[2-(furan-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carboxylic acid ( 2 ), 1-[2-(furan-2-yl)-2-oxoethyl]pyrrolidin-2-one ( 3 ) and 1-[2-(furan-2-yl)-2-oxoethyl]piperidin-2-one ( 4 ) on the basis of their 1D- and 2D-NMR, and HR-MS data. The absolute configurations of compounds 1 and 2 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) data. Additionally, four known compounds, 5 – 8 , were also isolated.

Description: Two new chemical constituents, one new steroid, neoveratrenone ( 1 ), and one new glycerol ester, 1-[11-(ferulyloxy)undecanoyl)]glycerol ( 2 ), were isolated and characterized from the roots and rhizomes of Veratrum dahuricum ( Turcz .) Loes . f., together with five known compounds, i.e. , hexacosanoic acid 2,3-dihydroxypropyl ester ( 3 ), syringaresinol ( 4 ), prosapogenin A of dioscin ( 5 ), verapatulin ( 6 ), and oxyresveratrol ( 7 ). Their structures were established by extensive analysis of spectroscopic data as well as by comparison with literature reports. The compounds were evaluated for cytotoxic activity against three tumor cell lines of HepG-2, HeLa, and K562/S.

Description: Two unusual rearranged flavan derivatives with a rare bicyclo[3.3.1]non-3-ene-2,9-dione ring, tazettone A ( 1 ) and tazettone B ( 2 ), together with five known flavans, 3 – 7 , were isolated from the bulbs of Narcissus tazetta var. chinensis Roem . The structures of two new compounds were elucidated by spectroscopic analyses, including 1D- and 2D-NMR spectroscopy. All of the isolated compounds were evaluated for their cytotoxicities against four human tumor cell lines A549, HCT116, SK-BR-3, and HepG2. Compounds 1 and 2 were almost inactive against all tested cell lines, while compounds 3 – 7 exhibited moderate or weak cytotoxicities against the tested cell lines.

Description: Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. Exposure to some kinds of volatile organic compounds (VOCs) leads to lung inflammation, oxidative stress, and immune modulation. However, it is suspected that sub-chronic exposure to low-dose VOCs mixture induces or aggravates lung inflammation. To clarify the effect of this exposure on lung inflammatory responses, 40 male Kunming mice were exposed in four similar static chambers, 0 (control) and three different doses of VOCs mixture (groups 1–3). The concentrations of VOCs mixture were as follows: formaldehyde, benzene, toluene, and xylene 0.10 + 0.11 + 0.20 + 0.20 mg/m 3 , 0.50 + 0.55 + 1.00 + 1.00 mg/m 3 , 1.00 + 1.10 + 2.00 + 2.00 mg/m 3 , respectively, which corresponded to 1, 5, and 10 times of indoor air quality standard in China. After 90 consecutive days of exposure (2 h/day), oxidative stress markers in lung, cellular infiltration and cytokines, chemokine, neurotrophin in bronchoalveolar lavage fluid (BALF), and immunoglobulin (Ig) in serum were examined. VOCs exposure could increase significantly reactive oxygen species (ROS) in lung, the levels of interleukin-8 (IL-8), IL-4, eotaxin, nerve growth factor (NGF), and various types of leukocytes in BALF, IgE concentration in serum. In contrast, GSH to GSSG ratio and interferon-gamma were significantly decreased following the VOCs exposure. These results indicate that the VOCs mixture-induced inflammatory response is at least partly caused by release of the ROS and mediators from the activated eosinophils, neutrophils, alveolar macrophages and epithelial cells. © 2013 Wiley Periodicals, Inc. Environ Toxicol 2013.

Description: Sick building syndrome (SBS) is a set of several clinically recognizable symptoms reported by occupants of a building without a clear cause. Neuropathy target esterase (NTE) is a membrane bound serine esterase and its reaction with organophosphates (OPs) can lead to OP-induced delayed neuropathy (OPIDN) and nerve axon degeneration. The aim of our study was to determine whether there was a difference in NTE activity in the peripheral blood mononuclear cells (PBMCs) of Japanese patients with SBS and healthy controls and whether PNPLA6 (alias NTE) gene polymorphisms were associated with SBS. We found that the enzymatic activity of NTE was significantly higher ( P 〈 0.0005) in SBS patients compared with controls. Moreover, population with an AA genotype of a single nucleotide polymorphism (SNP), rs480208, in intron 21 of the PNPLA6 gene strongly reduced the activity of NTE. Fifty-eight SNP markers within the PNPLA6 gene were tested for association in a case–control study of 188 affected individuals and 401 age-matched controls. Only one SNP, rs480208, was statistically different in genotype distribution ( P = 0.005) and allele frequency ( P = 0.006) between the cases and controls (uncorrected for testing multiple SNP sites), but these were not significant by multiple corrections. The findings of the association between the enzymatic activity of NTE and SBS in Japanese show for the first time that NTE activity might be involved with SBS. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: The electrochemical properties of 24 1,4-dioxidoquinoxalin-2-yl ketone derivatives with varying degrees of anti- Chagas activity were investigated in the aprotic solvent dimethylformamide (DMF) by cyclic voltammetry and first-derivative cyclic voltammetry. For this group of compounds, the first reduction in DMF was either reversible or quasireversible and consistent with reduction of the N -oxide functionality to form the radical anion. The second reduction process for these compounds was irreversible under the conditions used. The reduction potentials correlated well with molecular structure. Substitution in the 3-, 6-, and 7- positions of the quinoxaline ring by electron-withdrawing substituents directly affected the ease of reduction and improved the biological activities of these compounds, whereas substitution by electron-donating groups had the opposite effect. The electrochemical results, when combined with previous work on their mechanism of action against Chagas disease and their measured anti- Chagas activities, indicated that the quinoxaline 1,4-dioxide system serves as a promising starting point for chemical modifications aimed at improving the T. cruzi activity via a possible bioreduction mechanism.

Description: 1-Thiacyclooct-4-yne (=5,6-didehydro-3,4,7,8-tetrahydro-2 H -thiocin; 9 ) can be prepared from thiocan-5-one ( 6 ) in three steps by applying the so-called selenadiazole method. The heterocyclic alkyne can be oxidized to the corresponding sulfoxide 16 and sulfone 17 . Due to their geometrical strain, all three cyclic alkynes show high reactivities in Diels Alder and 1,3-dipolar cycloadditions. Moreover, tetrathiafulvalenes can be prepared from 9 and 16 by the reaction with CS 2 .

Description: This review continues a general presentation of the principles of stereochemistry with special reference to medicinal compounds. Here, we explore stereoisomeric compounds characterized by a single or several stereogenic centers (often also called centers of chirality). The main focus will be on chiral tetrahedral structures, namely a ) tetracoordinate centers, and b ) tricoordinate centers where an electron lone pair plays the role of the fourth substituent, forming a tetrahedron. Following an overview of the main tetrahedral structures of interest in biological and medicinal stereochemistry, the review places emphasis on explaining the two dominant conventions, namely the d,l - and ( R , S )-convention, the latter being known as the CIP ( Cahn Ingold Prelog ) convention. The review ends with a discussion of reactions of stereoisomerization at stereogenic C-centers and its relevance to drug research.

Description: Three new furofuran lignans, (+)-4,4′- O -diangeloylpinoresinol ( 1 ), (+)-4,4′- O -diangeloylmedioresinol ( 2 ), and (+)-4,4′- O -diangeloylsyringaresinol ( 3 ), together with the known compound (+)-syringaresinol, were isolated from the MeOH extract of Rudbeckia laciniata. The structure elucidation of these compounds were based on 1D- and 2D-NMR, and HR-ESI-MS data. The additional structural evidence was obtained from alkaline hydrolysis of the compounds.

Description: Enantiomerically pure (+)-( S )-clopidogrel was prepared by solid-phase synthesis using the commercially available Wang resin. This method offers mild reaction conditions and provides the (+)-( S )-clopidogrel in overall 52% yield over six steps and with optical purity of 98.0% ee.

Description: Anticholinesterase pesticides have been widely used in agricultural and domestic settings and can be detected in the environment after long-term use. Although the acute toxic effects of chlorpyrifos and carbaryl have been well described, little is known about the chronic toxicity of the pesticides mixture. To investigate their chronic neurotoxicity, Wistar rats were exposed to chlorpyrifos, carbaryl, and their mixture (MIX) for 90 consecutive days. The activities of serum cholinesterase (ChE) as well as acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in nerve tissues were determined. Furthermore, the histopathological examination was carried out. The results showed that ChE activity significantly decreased in all treated rats except the rats treated with low dose carbaryl. Treatment with middle- and high-dose chlorpyrifos and MIX in rats significantly inhibited AChE activity in the central nervous tissues, whereas treatment with carbaryl alone did not. In sciatic nerve, AChE activity was significantly inhibited by high-dose carbaryl and MIX, but not by chlorpyrifos alone. No significant NTE inhibition was observed in all treatment groups. Histopathological examination revealed that both chlorpyrifos and MIX treatment induced hippocampal damage. However, no obvious hippocampal damage was found in carbaryl-treated rats. Carbaryl and MIX, but not chlorpyrifos alone, induced pathological damage of sciatic nerve. Taken together, all of the results indicated that chlorpyrifos and carbaryl have different toxicological target tissues in nervous system and showed corresponding effects in the nervous tissues, which may reflect the different sensitivity of central and peripheral nervous tissues to different pesticides individually and in combination. © 2013 Wiley Periodicals, Inc. Environ Toxicol 2013.

Description: ABSTRACT Bombyx mori is an important economic animal for silk production. However, it is liable to be infected by organophosphorus pesticide that can contaminate its food and growing environment. It has been known that organophosphorus pesticide including phoxim exposure may damage the digestive systems, produce oxidative stress and neurotoxicity in silkworm B. mori , whereas cerium treatment has been demonstrated to relieve phoxim-induced toxicity in B. mori . However, very little is known about the molecular mechanisms of midgut injury due to phoxim exposure and B. mori protection after cerium pretreatment. The aim of this study was to evaluate the midgut damage and its molecular mechanisms, and the protective role of cerium in B. mori following exposure to phoxim. The results showed that phoxim exposure led to severe midgut damages and oxidative stress; whereas cerium relieved midgut damage and oxidative stress caused by phoxim in B. mori . Furthermore, digital gene expression suggested that phoxim exposure led to significant up-regulation of 94 genes and down-regulation of 52 genes. Of these genes, 52 genes were related with digestion and absorption, specifically, the significant alterations of esterase, lysozyme, amylase 48, and lipase expressions. Cerium pretreatment resulted in up-regulation of 116 genes, and down-regulation of 29 genes, importantly, esterase 48, lipase, lysozyme, and α-amylase were up-regulated. Treatment with Phoxim + CeCl 3 resulted in 66 genes up-regulation and 39 genes down-regulation; specifically, levels of esterase 48 , lipase , lysozyme , and α- amylase expression in the midgut of silkworms were significantly increased. Therefore, esterase 48 , lipase , lysozyme , and α- amylase may be potential biomarkers of midgut toxicity caused by phoxim exposure. These findings may expand the application of rare earths in sericulture. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Epidemiological studies have shown that pollution derived from industrial and vehicular transportation induces adverse health effects causing broad ambient respiratory diseases. Therefore, air pollution should be taken into account when microbial diseases are evaluated. Environmental mycobacteria (EM) are opportunist pathogens that can affect a variety of immune compromised patients, which impacts significantly on human morbidity and mortality. The aim of this study was to evaluate the effect of residual oil fly ash (ROFA) pre-exposure on the pulmonary response after challenge with opportunistic mycobacteria by means of an acute short-term in vivo experimental animal model. We exposed BALB/c mice to ROFA and observed a significant reduction on bacterial clearance at 24 h post infection. To study the basis of this impaired response four groups of animals were instilled with (a) saline solution (Control), (b) ROFA (1 mg kg −1 BW), (c) ROFA and EM-infected ( Mycobacterium phlei , 8 × 10 6 CFU), and (d) EM-infected. Animals were sacrificed 24 h postinfection and biomarkers of lung injury and proinflammatory madiators were examined in the bronchoalveolar lavage. Our results indicate that ROFA was able to produce an acute pulmonary injury characterized by an increase in bronchoalveolar polymorphonuclear (PMN) cells influx and a rise in O 2 − generation. Exposure to ROFA before M. phlei infection reduced total cell number and caused a significant decline in PMN cells recruitment ( p  〈 0.05), O 2 − generation, TNFα ( p  〈 0.001), and IL-6 ( p  〈 0.001) levels. Hence, our results suggest that, in this animal model, the acute short-term pre-exposure to ROFA reduces early lung response to EM infection. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT The chronic toxicity of 12 compounds of parabens and their chlorinated by-products was investigated using 7-day Ceriodaphnia dubia test under static renewal condition in order to generate information on how to disinfect by-products of preservatives that are discharged in aquatic systems. The mortality and inhibition of reproduction tended to increase with increasing hydrophobicity and decreased with the degree of chlorination of parabens. The EC 50 values for mortality, offspring number, and first brood production ranged between 0.30–3.1, 0.047–12, and 1.3–6.3 mg L −1 , respectively. For the number of neonates, the most sensitive endpoint, the no-observed-effect concentration (NOEC) and lowest-observed-effect concentration (LOEC) values ranged from 0.63 to 10 mg L −1 and from 1.2 to 19 mg L −1 , respectively. Methylparaben (MP), benzylparaben (BnP), and dichlorinated BnP (Cl 2 BnP) elicited a significant decrease in offspring numbers even at their lowest concentration tested; the NOEC for these compounds was determined to be less than the lowest test concentration (1.3, 0.04, and 0.63 mg L −1 for MP, BnP, and Cl 2 BnP, respectively). Propylparaben (PP), chlorinated PP, isopropylparaben (iPP), and chlorinated iPP exhibited nonmonotonic concentration-dependent response; their NOEC and LOEC values could not be determined. The multivariate approach involving principal component analysis and hierarchical cluster analysis revealed four groups that corresponded to the toxicological profiles of parabens. Our results suggested that disinfection of parabens by chlorination could reduce aquatic toxicity of original compounds. The findings obtained in our study together with the data available on paraben concentrations in aquatic systems can be used to perform preliminary risk assessment by comparing the predicted environmental concentration (PEC) with the predicted no-effect concentration (PNEC) for the marine aquatic environment. The calculated PEC/PNEC ratios ranged from 0.0012 to 0.2, with the highest value observed in MP. This suggested that there are negligible environmental risks for aquatic organisms at current use levels. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Fish are relatively sensitive to changes in their surrounding environment, including increasing pollution. Therefore, the present study was undertaken to evaluate the impact of contamination with the pendimethalin-based herbicide; Stomp ® 50% EC (50% pendimethalin as emulsive concentrate) on adults of the monosex Nile tilapia Oreochromis niloticus L. A total of 260 fish with body weights of 90 ± 5.0 g were used in the determination of the 96-h LC 50 value and of the impacts of acute exposure to pendimethalin on physiological parameters, and oxidative stress and antioxidant biomarkers. The 96-h median lethal concentration (96-h LC 50 ) value of pendimethalin for monosex Nile tilapia was determined as 4.92 mg/L. Abnormal behavioral responses of the fish and the toxic symptoms of pendimethalin exposure are described. Acute exposure to pendimethalin induced leukocytosis, hyperglobulinemia, and hyperglycemia, but resulted in nonsignificant changes in other hemato-biochemical parameters. Moreover, pendimethalin increased lipid peroxidation (LPO) and decreased levels of reduced glutathione and antioxidant enzymes; superoxide dismutase, catalase, and glutathione reductase in both liver and gill tissues, in a time-dependent manner, with maximum alterations observed in the gills rather than the liver. We conclude that although pendimethalin is moderately toxic, it does not cause hepatorenal toxicity. However, this herbicide pollutant induces major disturbances to the antioxidant system; induction of oxidative stress and LPO is the proposed toxicodynamic pathway for such stress. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT A rapid cyanobacterial bloom of Cylindrospermopsis raciborskii (3.2 × 10 4 filaments/mL) was detected early November, 2012, in the Fancsika pond (East Hungary). The strong discoloration of water was accompanied by a substantial fish mortality (even dead cats were seen on the site), raising the possibility of some toxic metabolites in the water produced by the bloom-forming cyanobacteria ( C. raciborskii ). The potential neuronal targets of the toxic substances in the bloom sample were studied on identified neurons (RPas) in the central nervous system of Helix pomatia . The effects of the crude aqueous extracts of the Fancsika bloom sample (FBS) and the laboratory isolate of C. raciborskii from the pond (FLI) were compared with reference samples: C. raciborskii ACT 9505 (isolated in 1995 from Lake Balaton, Hungary), the cylindrospermopsin producer AQS, and the neurotoxin (anatoxin-a, homoanatoxin-a) producer Oscillatoria sp. (PCC 6506) strains. Electrophysiological tests showed that both FBS and FLI samples as well the ACT 9505 extracts modulate the acetylcholine receptors (AChRs) of the neurons, evoking ACh agonist effects, then inhibiting the ACh-evoked neuronal responses. Dose–response data suggested about the same range of toxicity of FBS and FLI samples (EC 50  = 0.397 mg/mL and 0.917 mg/mL, respectively) and ACT 9505 extracts (EC 50  = 0.734 mg/mL). The extract of the neurotoxin-producing PCC 6506 strain, however, proved to be the strongest inhibitor of the ACh responses on the same neurons (EC 50  = 0.073 mg/mL). The presented results demonstrated an anatoxin-a-like cholinergic inhibitory effects of cyanobacterial extracts (both the environmental FBS sample, and the laboratory isolate, FLI) by some (yet unidentified) toxic components in the matrix of secondary metabolites. Previous pharmacological studies of cyanobacterial samples collected in other locations (Balaton, West Hungary) resulted in similar conclusions; therefore, we cannot exclude that this chemotype of C. raciborskii which produce anatoxin-a like neuroactive substances is more widely distributed in this region. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT In previous work, our laboratory developed a Drosophila model for studying the adverse effects of fungal volatile organic compounds (VOCs) emitted by growing cultures of molds. In this report, we have extended these studies and compared the toxic effects of fungal VOCs emitted from living cultures of four molds isolated after Hurricane Katrina from a flooded home in New Orleans. Strains of Aspergillus , Mucor, Penicillium , and Trichoderma were grown with wild-type larvae and the toxic effects of volatile products on the developmental stages of Drosophila larvae were evaluated. Furthermore, heterozygous mutants of Drosophila carrying the apoptotic genes, reaper and dronc , were used to assess the role of apoptosis in fungal VOCs mediated toxicity. Third-instar larvae of Drosophila carrying these apoptotic genes were exposed to fungal VOCs emitted from growing mold cultures for 10 days. The larval strains carrying apoptopic genes survived longer than the control wild type larvae; moreover, of those that survived, heterozygous reaper and dronc strains progressed to pupae and adult phases more rapidly, suggesting that fungal VOCs may induce apoptotic changes in flies. These data lend support to the use of Drosophila as an inexpensive and genetically versatile toxicological model to investigate the mechanistic basis for some of the human illnesses/symptoms associated with exposure to mold-contaminated indoor air, especially after hurricanes. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Triethyleneglycol-dimethacrylate (TEGDMA) is a monomer and widely used in dental composite resins. TEGDMA has been found to exhibit cytotoxicity and genotoxicity on many cells. However, little is known about the potential toxicological implications of TEGDMA on murine macrophage cell line RAW264.7. In this study, TEGDMA demonstrated a cytotoxic effect to RAW264.7 cells in a concentration- and time-dependent manner ( p  〈 0.05). TEGDMA was found to induce two modes of cell death in a concentration-dependent manner ( p  〈 0.05). TEGDMA-induced cell apoptosis was demonstrated by the increase in the portion of sub-G0/G1 phase and DNA ladder formation. In addition, TEGDMA exhibited genotoxicity via a dose-related increase in the numbers of micronucleus and DNA strand breaks ( p  〈 0.05). Furthermore, the activation of caspase-3, −8, and −9 were generated by TEGDMA in a dose-dependent manner ( p  〈 0.05). These results indicated that cytotoxicity and genotoxicity induced by TEGDMA in macrophages may be via DNA damage and caspase activation. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT Asian sand dust (ASD), a type of particulate matter found in Asia, migrates to East Asia. The increased airborne spread of ASD has led to concerns regarding possible adverse health effects. Our group previously reported that ASD induces lung inflammation in mice, but it is still unclear whether ASD affects lymphoid organs. In this study, we investigated the effect of ASD on splenocytes in a mouse model of ASD exposure. ICR mice were intratracheally administered a single dose of normal saline (control) or ASD and were subsequently sacrificed 1 or 3 days later. TNF-α production in bronchoalveolar lavage fluids was higher at day 1, but not at day 3, after ASD administration. The enzyme-linked immunosorbent assay results showed that ASD administration increased mitogen-induced IL-2, TNF-α, and IL-6 production in splenocytes. Additionally, cell viability assay showed enhanced splenocyte proliferation at day 3, but not at day 1, after ASD administration. The electrophoretic mobility shift assay results demonstrated that nuclear factor κB (NF-κB) was activated in splenocytes on day 3, but not on day 1. In particular, NF-κB activation was detected in CD4 + and CD11b + cells on day 3. These results suggest that ASD induces subacute inflammatory responses with NF-κB activation in the spleen, in contrast to acute inflammation in the lungs. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: ABSTRACT We hypothesize that citreoviridin (CIT) induces DNA damage in human liver-derived HepG2 cells through an oxidative stress mechanism and that N -acetyl- l -cysteine (NAC) protects against CIT-induced DNA damage in HepG2 cells. CIT-induced DNA damage in HepG2 cells was evaluated by alkaline single-cell gel electrophoresis assay. To elucidate the genotoxicity mechanisms, the level of oxidative DNA damage was tested by immunoperoxidase staining for 8-hydroxydeoxyguanosine (8-OHdG); the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH) were examined; mitochondrial membrane potential and lysosomal membranes' permeability were detected; furthermore, protective effects of NAC on CIT-induced ROS formation and CIT-induced DNA damage were evaluated in HepG2 cells. A significant dose-dependent increment in DNA migration was observed at tested concentrations (2.50–10.00 µM) of CIT. The levels of ROS, 8-OHdG formation were increased by CIT, and significant depletion of GSH in HepG2 cells was induced by CIT. Destabilization of lysosome and mitochondria was also observed in cells treated with CIT. In addition, NAC significantly decreased CIT-induced ROS formation and CIT-induced DNA damage in HepG2 cells. The data indicate that CIT induces DNA damage in HepG2 cells, most likely through oxidative stress mechanisms; that NAC protects against DNA damage induced by CIT in HepG2 cells; and that depolarization of mitochondria and lysosomal protease leakage may play a role in CIT-induced DNA damage in HepG2 cells. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Description: 4-Arylisocoumarins (=4-aryl-1 H -2-benzopyran-1-ones) 6 were prepared from 2-(1-aryl-2-methoxyethenyl)-1-bromobenzenes 1 . Successive treatment of these bromo styrenes with BuLi and 1-formylpiperidine gave a mixture of ( E )- and ( Z )-2-(1-aryl-2-methoxyethenyl)benzaldehydes 2 . Hydrolysis of ( Z )-isomers with conc. HBr, followed by pyridinium chlorochromate (PCC) oxidation of the resulting 1 H -2-benzopyran-1-ol derivatives 4 (and 5 ), afforded the desired products.

Description: Phytochemical investigation of the aerial parts of Gymnema sylvestre led to the isolation of two known oleanane-type triterpenes, 1 and 3 , five new acylated derivatives, 2, 4 , and 5 – 7 , and a new lupane-type triterpene, 8 . The structures and relative configurations of these compounds were elucidated by spectroscopic analyses, including 1D- and 2D-NMR spectroscopy and mass spectrometry, and by the comparison of their NMR data with those of related compounds.

Description: Two new indole alkaloids, 5-oxodolichantoside ( 1 ) and deglycocadambine ( 2 ), were isolated from the twigs and leaves of Emmenopterys henryi , together with four known indole alkaloids and five known iridoids. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses, including 1D- and 2D-NMR experiments, and confirmed by single-crystal X-ray diffraction studies. This is the first report on the isolation of indole alkaloids from this species. The indole alkaloids were evaluated for their cytotoxic activities against five human cancer lines.

Description: Six new biscembranoids, namely, sarcophytolides G–L ( 1 – 6 , resp.), together with six known analogs, were isolated from a marine soft coral Sarcophyton elegans. The structures of the new compounds were established on the basis of 1D- and 2D-NMR (COSY, HSQC, HMBC, and NOESY) spectroscopic analysis together with the aid of MS, CD, and IR data. The unusual isobiscembranoid sarcophytolide G ( 1 ) was found for the first time in the genus Sarcophyton.

Description: Two new trijugin-type limonoids, cipatrijugins G and H ( 1 and 2 , resp.) along with four known limonoids, were isolated from the leaves of Cipadessa cinerascens. All structures were elucidated on the basis of spectroscopic analyses, including IR, 1D- and 2D-NMR, and ESI-MS and HR-ESI-MS techniques.

Description: The total synthesis of crassalactone A ( 1 ) has been achieved in twelve steps starting from commercially available 1,5- D -gluconolactone. Still Gennari olefination, one-pot deprotection, and lactonization are the key reactions involved in the synthesis.

Description: Phytochemical investigation of the 70% EtOH extract from the stem bark of Dysoxylum lukii led to the isolation of three new ergostane steroids, (3 β )-3,20-dihydroxyergosta-5,24(28)-dien-7-one ( 1 ), (3 β ,4 β ,7 α )-ergosta-5,24(28)-diene-3,4,7-triol ( 2 ), and (3 β ,7 α )-3,20-dihydroxyergosta-5,24(28)-dien-7-yl acetate ( 3 ), together with the known compound (3 β ,4 β )-ergosta-5,24(28)-diene-3,4,20-triol ( 4 ). Their structures were elucidated on the basis of extensive 1D- and 2D-NMR (COSY, HMQC, HMBC, and NOESY) analyses.

Description: A novel ‘click ligation’ strategy for the stereoselective synthesis of a medium-size library of structurally complex and functionally diverse oxazolone peptidomimetics, which contain α -acylamino carboxamide or β -amido ketone residues, is presented. Most of these molecules have lipophilicity constant values (log P ) in the qualifying range for cell permeability, and that indicates the possibilities of these new molecules to be used in the search for potential inhibitors for a broad spectrum of enzymes.

Description: An efficient one-pot procedure for the synthesis of 3-amino-6-aryl-2-phenylpyrazolo[3,4- d ]pyrimidine derivatives, through the reaction of aldehydes, malononitrile, benzamidine hydrochloride, and hydrazine hydrate in the presence of basic alumina-supported sodium acetate (AcONa/Al 2 O 3 ) under reflux conditions, is reported. This protocol has some advantages, including the use of a simple and one-pot synthetic approach to attain pyrazolo[3,4- d ]pyrimidine directly from four readily available starting materials, simple workup, high overall yields of the products, and the simultaneous conversion of a NO 2 to an amino group, offering an opportunity to synthesize more complex structures.

Description: Investigation of the wood of Cunninghamia konishii resulted in the isolation and characterization of one new abietane diterpenoid, (6 α ,7 β )-7,8-epoxy-6-hydroxyabieta-9(11),13-dien-12-one ( 1 ), and two new labdane diterpenoids, (12 R )-12-hydroxylabda-8(17),13(16),14-trien-19-oic acid ( 2 ) and (12 R )-12-hydroxylabda-8(17),13(16),14-trien-18-oic acid ( 3 ). The structures of these new compounds were elucidated by analysis of their spectroscopic data.

Description: The first example of the stereoselective synthesis of ( Z )- and ( E )-allyl aryl sulfides and selenides from Baylis Hillman acetates under neutral conditions in H 2 O by supramolecular catalysis involving β -cyclodextrin is reported. β -Cyclodextrin can be recovered and reused. The reaction is very efficient in providing allyl aryl sulfides and selenides in good-to-excellent yields with clean reaction profiles under mild reaction conditions.

Description: Ten new monoterpenoid indole alkaloids, ochroborines A and B ( 1 and 2 , resp.), 10-hydroxyisovallesiachotamine ( 3 ), 10-hydroxyisositsirikine ( 4 ), 10,11-dimethoxysitsirikine ( 5 ), 10-methoxyapoyohimbine ( 6 ), 10-hydroxyakuammidine ( 7 ), akuammidine 17- O - β - D -glucoside ( 8 ), 15 α -hydroxyapparicine ( 9 ), and 15 α -hydroxy-10-methoxyapparicine ( 10 ), and 24 known alkaloids were isolated from leaves and twigs of Ochrosia borbonica J. F. Gmel . These structures were elucidated based on 1D- and 2D-NMR, FT-IR, UV, and MS data. 10-Hydroxyisovallesiachotamine ( 3 ), ellipticine, and 10-methoxyellipticine showed cytotoxic activities against five human cancer cell lines.

Description: Two new diterpeniods, euphebracteolatins A and B ( 1 and 2 , resp.) were isolated from Euphorbia ebracteolata Hayata , along with two known ones (3 R )- ent -rosa-1(10),15-dien-3 α -ol ( 3 ) and yuexiandajisu D ( 4 ). The structures were established by extensive spectroscopic analyses and comparison with literature data.

Description: By the year 1913, a number of revolutionary events had begun to transform the landscape of physics. In 1900, Max Planck (1858–1947) had proposed that energy radiated in quanta or packets. The announcement of the photoelectric effect in 1905 by an unassuming Swiss patent worker by the name of Albert Einstein (1879–1955) clearly implicated that light energy, or the photon, later coined by Gilbert N. Lewis (1875–1946) in 1926, was also quantized and showed unprecedented particle-like properties. More startling was the discovery by Ernest Rutherford (1871–1937) who demonstrated that the atom consisted of a hard positive center surrounded by electrons. Niels Bohr (1885–1962), then a young postgraduate, was deeply involved in understanding the structure of the atom. He needed physical or experimental evidence to substantiate his intuitive ideas. Ironically, that evidence had already been published in the year of his birth by Johann J. Balmer (1825–1898), a Swiss mathematics teacher at a secondary school for girls.

Description: An efficient approach for the preparation of functionalized 5-aryl-3-(methylsulfanyl)-1 H -pyrazoles 2 is described. This three-component reaction between benzaldehydes 1 , NH 2 NH 2 ⋅H 2 O, and 1,1-bis(methylsulfanyl)-2-nitroethene proceeds in EtOH under reflux conditions in good-to-excellent yields. The structures of 2 were corroborated spectroscopically (IR, 1 H- and 13 C-NMR, and EI-MS). A plausible mechanism for this type of reaction is proposed ( Scheme 2 ).

Description: This report provides a description of an efficient and simple procedure for the synthesis of substituted cyclopentadienes via a one-pot three-component reaction of cyclohexyl isocyanide, diethyl acetylenedicarboxylate and (arylmethylidene)malononitriles in H 2 O under ultrasonic irradiation. The remarkable advantages are the simplicity of the experimental procedures, high yields, short reaction times, and avoidance of organic solvents.

Description: An efficient synthesis of alkyl 5-(alkylimino)-3-aryl(alkyl)-2-(dicyanomethylene)-4-hydroxythiazolidine-4-carboxylates, containing polarized C C bonds, via reaction of malononitrile, arylisothiocyanates, and the Nef -isocyanide adducts, under basic conditions, is described.

Description: 5-(2-Cyanoethyl)-1,1′-biphenyl-2-carboxylates were prepared by regioselective formal [3+3] cyclocondensations of 1,3-bis[(trimethylsilyl)oxy]buta-1,3-dienes.

Description: A convenient procedure for the preparation of a new type of thiophthalides, 3-alkoxybenzo[ c ]thiophen-1(3 H )-ones 4 and 9 has been developed. Thus, 1-(dialkoxymethyl)-2-lithiobenzenes, generated by Br/Li exchange between 2-bromo-1-(dialkoxymethyl)benzenes 1 and 6 , and BuLi, react with isothiocyanates to afford N -substituted 2-(dialkoxymethyl)benzothioamides 2 and 7 , which, on treatment with a catalytic amount of TsOH⋅H 2 O, give N -substituted 3-alkoxybenzo[ c ]thiophen-1(3 H )-imines 3 and 8 . The latter are hydrolyzed under acidic conditions to the desired products 4 and 9 , respectively.

Description: 3-Alkyl/aryl-3-hydroxyquinoline-2,4-diones were reduced with NaBH 4 to give cis -3-alkyl/aryl-3,4-dihydro-3,4-dihydroxyquinolin-2(1 H )-ones. These compounds were subjected to pinacol rearrangement by treatment with concentrated H 2 SO 4 , resulting in 4-alkyl/aryl-3-hydroxyquinolin-2(1 H )-ones. When a benzyl (Bn) group was present in position 3 of the starting compound, its elimination occurred during the rearrangement, and the corresponding 3-hydroxyquinolin-2(1 H )-one was formed. The reaction mechanisms are discussed for all transformations. All compounds were characterized by IR, 1 H- and 13 C-NMR spectroscopy, as well as mass spectrometry.

Description: Three new hasubanan alkaloids, hernsubanines A–C ( 1 – 3 , resp.), were isolated from the whole plants of Stephania hernandifolia. Their structures were elucidated on the basis of physical and spectroscopic data. In in vitro tests for cytotoxic activity against two human cancer cell lines, A 549 and K 562, compound 1 did not exhibit any cytotoxicity.

Description: The first asymmetric total synthesis of (−)-ligustiphenol is reported. The key step was conducted by exploiting a steric hindrance effect to control the formation of the adduct in a nucleophilic α -Li-phenolate addition reaction to the intermediate α -oxo (−)-menthyl ester. The synthesis is concise and feasible for the construction of analogous compounds and investigation of their biological activity.

Description: A new, one-pot condensation of aldehydes, enolizable ketones and esters, AcCl, and MeCN, in the presence of Fe 3 O 4 nanoparticles (nano-Fe 3 O 4 ) as an efficient catalyst, for the preparation of β -acetamido carbonyl compounds at room temperature is described.

Description: A simple and efficient enantioselective synthesis of (6 S )-5,6-dihydro-6-[(2 E )-4-oxo-6-phenylhex-2-en-1-yl]-2 H -pyran-2-one (=( S )-rugulactone) has been accomplished. The synthesis started from commercially available propane-1,3-diol and ethyl 3-phenylpropanoate and involve the Horner Wadsworth Emmons ( HWE ) and Still 's modified HWE olefinations, and Sharpless asymmetric epoxidation.