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Nitrogen- or oxygen-containing organic compounds which have significant antifungal activity, twenty one novel nitrogen or oxygen-containing (E)-3-acyl-5-(methoxyimino)-1,5-dihydrobenzo[e][1,2]oxazepin-4(3H)-one analogues were designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR and HRMS. Preliminary bioassay showed that most of them exhibited certain-to-good antifungal activity. Compounds 5k-2, 5n, 5p and 5r exhibited over 80% inhibitory rate against Sclerotinia sclerotiorum at 50 μg/mL, and 5r exhibited good antifungal activity against S. sclerotiorum with EC50 of 7.21 μg/mL. Compounds 5a and 5r also showed over 90% inhibition against Botrytis cinerea. In particular, 5r showed significant higher activity with the lowest EC50 of 7.92 μg/mL than the positive control trifloxystrobin (21.96 μg/mL) and azoxystrobin (9.43 μg/mL). Providing a practical method for the synthesis of new scaffolds 1,2-Benzoxazepinone and systematically investigate their antifungal activity.

A highly enantioselective cyclopropanation to synthesize pyrimidine-substituted diester D–A cyclopropanes is reported. Various N1-vinylpyrimidines react well with phenyliodonium ylides, delivering chiral cyclopropanes in up to 97% yield with up to 99% ee. Through simple [3+2] annulation with benzaldehyde or ethyl glyoxylate, different chiral pyrimidine nucleoside analogues with a sugar ring could be obtained.

The mode of action is the basis for the rational design of the novel agrochemicals. 3-(4-Methyl-1,2,3-thiadiazolyl)-6-trichloromethyl [1,2,4]triazolo [3,4-b][1,3,4]thiadiazole (YZK-C22) is a novel fungicide candidate. The aim of this study was identification of the mechanism of YZK-C22 against fungi. The results indicated that YZK-C22 inhibited the mycelial growth and spore germination of Botrytis cinerea. Total 56 differentially expressed proteins (DEPs) including 27 up regulated and 29 down regulated proteins were identified by isobaric tags for relative and absolute quantification (iTRAQ). The DEPs mainly concentrated on metabolic pathways, and the results were consistent across the studies of RNA and protein platforms. The pyruvate kinase (PK) activity in the glycolytic pathway was inhibited over 50% by 20 μg/mL of YZK-C22. Molecular docking analysis also validated that YZK-C22 could dock into the active centre of the PK instead of phosphoenolpyruvate. In summary, iTRAQ was an effective way for target identification of YZK-C22.

Background Lactic acid bacteria with probiotic and antibacterial properties were isolated from the vagina of healthy cows. The purpose of the study is to isolation and screening of lactic acid bacteria strains with antibacterial properties from the vagina of healthy cows, which could be used to treat cow vaginal inflammation. Results Isolation and identification of eight dominant lactic acid bacteria strains from 55 isolates was performed using classic microbiology methods and fermentation engineering. Eight strains were selected that had no spores and capsules, exhibited strong acid production capacity (pH Lactobacillus johnsonii (SQ0048) had the lowest pH (4.32) and shortest acid-producing time (8 h). L. johnsonii (SQ0048) could produce hydrogen peroxide, inhibit the growth of Staphylococcus aureus and Escherichia coli and adhere to the vaginal epithelial cells of cows. The average number adhering to each cell was 304±2.67. Bacteriocin genes were detected in L. johnsonii (SQ0048), and the bacteriocin gene of a positive clone of this strain was 100% similar to that of Lactobacillus johnsonii NCC 533 (NC_005362.1). Expression of the bacteriocin genes had inhibitory activity against S. aureus and E. coli. Conclusions These advantages indicate that SQ0048 is a promising candidate for use in antimicrobial preparations.

Natamycin, an important 26-member tetraene macrolide antifungal antibiotic, is widely used as antifungal agent in the food industry and medical fields. However, low yields of the currently used production strains limit its wider applications. To improve the productivity of natamycin-producing strains, we co-expressed the Vitreoscilla hemoglobin gene vgb in Streptomyces gilvosporeus with two genes that constitute part of the natamycin biosynthesis gene cluster: pimE (encoding a signalling protein) and pimM (encoding a positive regulator). Both genes were cloned and ligated into the shuttle vector pIMEP under the control of the strong, constitutive Perm promoter, and integrated into the chromosome of S. gilvosporeus via conjugation. Natamycin production was increased 40.3% upon overexpression of pimE and pimM. Furthermore, in order to alleviate oxygen limitation, we additionally expressed vgb in the pimE and pimM over-expressing strain, yielding S. gilvosporeus/pIMEP::pimE::pimM::vgb, which showed a further 55.7% improvement for natamycin production compared to that of the recipient strain. In conclusion, co-expression of pimE and pimM with vgb led to markedly increased natamycin production, thus pointing out a potential strategy for enhancing the microbial production of other antibiotics as well.

Palladium-catalyzed regio- and enantioselective allylic amination of aliphatic Morita-Baylis-Hillman (MBH) adducts with N-heteroaromatic nucleophiles (e.g., benzimidazole, 4,5-diphenylimidazole, benzotriazole, and purines) was achieved by using a spiroketal-based diphosphine (SKP) ligand, and afforded a range of chiral, branched N-allyl products with high selectivity.

An efficient route to construct chiral cyclopropyl purine nucleoside analogues has been established via the catalytic asymmetric Michael-initiated ring-closure reactions of α-purine acrylates with α-bromo-carboxylic esters. Using (DHQD)2AQN as the catalyst, various chiral cyclopropyl purine nucleoside analogues with a chiral quaternary stereocenter were obtained in 72-98% yields, excellent diastereoselectivities, and 93-97% ee. Through simple functional group transformations, diverse chiral cyclopropyl purine nucleosides with hydroxymethyl group or carboxyl group were obtained.

Antioxidant potencies of an ethanolic extract and its components from Lepidium latifolium were investigated. In this study, we found that the ethyl acetate soluble fraction of L. latifolium was a rich source of antioxidant, resulting from its high total phenolic content. To determine the antioxidant components of the ethyl acetate fraction, a bioassay-guided fractionation approach using 1,1-diphenyl-2-picrylhydrazyl, 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulfonate), and ferric reducing antioxidant power assays were conducted. Nine compounds were isolated and their structures were identified by MS and NMR spectral data and comparison to reported data. They are Quercetin-3-O-β-d-sophoroside-7-O-α-l-rhamnoside (1), Apetalumoside B6 (2), Kaempferol-3-O-β-d-glucopyranosyl-(1-2)-β-d-glucopyranoside-7-O-β-d-glucopyranoside (3), Kaempferol-7-O-α-l-rhamnopyranoside (4), Kaempferol-3-O-β-d-glucopyranoside-7-O-α-l-rhamnopyranoside (5), Kaempferol-3-O-(2-O-feruloyl-β-d-glucopyranosyl-(1-2)-β-d-glucopyranoside)-7-O-glucopyranoside (6), Kaempferol-3-O-β-d-sophoroside-7-O-α-l-rhamnoside (7), Kaempferol-3-O-robinoside-7-O-(2″″-(E)-feruloyl)-sophoroside (8), Quercetin-3-O-(2,6-di-O-β-d-glucopyranosyl)-β-d-glucopyranoside-7-O-α-l-rhamnopyranoside (9), compounds 1, 2, 4, and 8 had potent free radical scavenging activity. The IC50 values of these compounds were 9.8–12.3 and 7.4–31.4 μg/mL in DPPH and ABTS assays, respectively. The results indicate that L. latifolium is a potential natural source of antioxidants to treat several diseases related to oxidant by-products of human metabolism.

The aim of the present study was to evaluate the antiproliferative effect of phenylpropanoids isolated from the n-BuOH-soluble fraction of an ethanolic extract of Lagotis brevituba Maxim. The phenylpropanoids were identified as echinacoside, lagotioside, glucopyranosyl(1-6)martynoside, plantamoside, and verbascoside. Three of the compounds, lagotioside, glucopyranosyl(1-6)martynoside, and plantamoside, were isolated from L. brevituba for the first time. The antiproliferative activity of the isolates was evaluated in human gastric carcinoma (MGC-803), human colorectal carcinoma (HCT116), human hepatocellar carcinoma (HepG2), and human lung cancer (HCT116) cells using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Plantamoside showed promising activity against MGC-803 cells, with a half maximal inhibitory concentration value of 37.09 μM. The mechanism of the pro-apoptosis effect of plantamoside was then evaluated in MGC-803 cells. Changes in cell morphology, including disorganization of the architecture of actin microfilaments and formation of apoptotic bodies, together with cell cycle arrest in G2/M phases, were observed after treatment of plantamoside. The antiproliferative and pro-apoptotic effects were associated with a decrease in the ratio of Bcl-2/Bax and reduced mitochondrial membrane potential, which was accompanied by the release of reactive oxygen species and Ca2+ into the cytoplasm. Taken together, the results indicated that plantamoside promotes apoptosis via a mitochondria-dependent mechanism. Copyright © 2017 John Wiley & Sons, Ltd.

A combined palladium- and photoredox-catalyzed monoselective arylation of 6-arylpurine nucleosides has been developed by employing purine as a directing group via the photoredox reaction, and many functional groups are well tolerated in this direct C-H arylation condition. Various of functionalized purines (nucleosides) which are potentially of great importance in medicinal chemistry could be obtained under visible light irradiation at room temperature within 4 h.

Diarylethene photoswitches based on the natural nucleoside deoxyadenosine were designed and synthesized. In aqueous solution, some of them exhibited good photochromic properties, including clear changes in color upon irradiation at 365 nm, red-shifts of the absorption wavelength, with good fatigue resistance, thermal stability, conversion efficiency, and base-pairing properties.

A convenient and efficient synthesis of multi-substituted thiazole-containing tetrahydropyridine moieties was reported using the phosphine-catalyzed Aza–Rauhut–Currier reaction with excellent yields and diastereoselectivity. Thiazole-containing tetrahydropyridines were further transformed into the corresponding piperidine derivatives. The biological activity of the title compounds was explored; they exhibited moderate insecticidal activity against Aphis laburni Kaltenbach at 100 μg mL. A 3D QSAR model accurately predicted the insecticidal activity of the structurally diverse set of test compounds. Thiazole-containing tetrahydropyridines were active against normal fungi and also had good activity against resistant fungi mutations without cross resistance; thus, these compounds will be valuable for resistance management. The predicted potential fungicidal target of the title compounds is fumarate reductase.

The difference of cold resistance between aboveground and underground parts was compared by measuring the growth and cold-resistance physiology of dormancy-released Sedum aizoon L. seedling with sprout at -5, 0 and 5 degrees Celsius respectively. The results showed that with the decreasing temperature, the plant height and root length all showed a downward trend, and the plant height decreased more than root length. The aboveground fresh weight showed an upward trend, while the underground fresh weight showed a downward first and then upward trend. The relative electrical conductivity (REC), tissue water content, total soluble sugar and free proline content all showed an upward trend, while malondialdehyde (MDA) content showed a downward trend in leaves. The content of soluble protein showed a downward first and then upward trend in leaves. The changing trend of roots was the same as leaves in REC, total soluble sugar and soluble protein content, but the REC of roots increased less than leaves. There was no significant change in tissue water content, free proline and MDA content in roots. At the same low temperature, roots were all higher than leaves in the content of total soluble sugar and soluble protein, while the tissue water content and MDA content were the contrary. In conclusion, the cold resistance of the underground part was stronger than aboveground part in Sedum aizoon L. seedling with sprout.

An efficient method to construct chiral cyclopropyl pyrimidine carbocyclic nucleoside analogues bearing a quaternary center was developed via asymmetric Michael-initiated cyclopropanation. The axis chirality was observed in cyclopropyl pyrimidine carbocyclic nucleoside analogues for the first time, which was caused by the rotationally restricted N C bond in N-COPh moiety. Using (DHQD)2AQN as the organocatalyst, diverse cyclopropyl pyrimidine carbocyclic nucleoside analogues were generated in 76–93% yields and 73–96% ee.

A molecular design approach was used in our laboratory to guide the development of imidazole-based fungicides. Based on homology modeling and molecular docking studies targeting the cytochrome P450-dependent sterol 14α-demethylase, 3,4-dichloroisothiazole-based imidazoles showed great potential. Several such compounds were then rationally designed, synthesized, characterized, and their antifungal activities were evaluated. Bioassay results showed that compounds such as ( R)-11, ( R)-12, and ( S)-11 have commendable, broad-spectrum antifungal activities that are comparable to those of commercial products. Based on Q-PCR testing and microscopy observations, the imidazole derivatives affect fungal cell wall formation through the inhibition of the BcCYP51 expression system. These findings strongly suggest that the mode of action of these imidazole compounds is similar to that of tioconazole and imazalil. This report indicates that this molecular design strategy is not only practical but productive.

Push–pull-type purine nucleoside-based fluorescent sensor L1 bearing a chelating N,N-bis(2-pyridylmethyl)amine group at the C6 position was designed and synthesized. Sensor L1 showed clear and selective detection of Pd2+ in aqueous buffer, and it is the first “on–off”-type purine nucleoside-based fluorescent sensor for Pd2+.

A perylene diimide (PDI) based fluorescence chemosensor (PDI-1) for Pd2+ was prepared. PDI-1 showed a remarkable fluorescence enhancement (over 120-fold) in the presence of Pd2+ in mixed aqueous media with high selectivity and sensitivity. Moreover, the dramatically ‘off–on’ fluorescence response concomitantly induced the obvious color change from dark purple to brilliant pink, which could also be identified by naked eyes easily. The low limit for Pd2+ detection was found to be as small as 10−9 mol/L. Hence, PDI-1 is a highly promising fluorescent chemosensor for the direct determination of residual Pd2+ in chemical medicines and environment samples.

The one-pot and direct synthesis of 7,9-dialkylpurin-8-one analogues with broad substrate scope has been developed. This copper-catalyzed C-H oxidation reaction could avoid multistep synthesis of quaternary ammonium salts and expand the scope of halogenated alkanes. Moreover, benzimidazole derivatives are also applicable in the catalytic system.

Objective: The inhibition of cyclooxygenase-2 (COX-2) by nonsteroidal anti-inflammatory drugs may prevent the occurrence and decrease the incidence of gastrointestinal malignant neoplasms. This study was designed to detect the expression patterns of COX-2 in human normal, benign, and malignant pancreatic tissues and investigate the correlation between the expression of COX-2 and Bcl-2 in malignant pancreatic tissues, which may help to demonstrate the functional role of COX-2 and Bcl-2 in pancreatic carcinogenesis and carcinoma development. Methods: Immunohistological analysis of COX-2 and Bcl-2 was performed on different human pancreatic samples, including malignant tissues. The correlation between COX-2 and Bcl-2, as well as clinic-pathological characteristics of pancreatic carcinoma was evaluated by statistic analysis. Results: COX-2 and Bcl-2 proteins were detected in 22 of 30 (73.3%) and 20 of 30 (66.7%) malignant pancreatic tissues, which were higher than those in normal and benign tissues (P 0.05). Conclusion: COX-2 protein is over-expressed in human malignant pancreatic tissues. The co-expression of COX-2 and Bcl-2 might play an important role in the regulation of apoptosis of pancreatic carcinoma cells.

The relation between the surface acidity of H-mordenite synthesized in nonaqueous solvents (HNAM) and H-mordenite synthesized in aqueous solvents (HAM) and isomerization of ortho -xylene was investigated with techniques of pulsed microreactor (carrier H 2 ), temperature programmed desorption of NH 3 (t.p.d.), and pulsed poisoning experiment of 2,6-dimethylpyridine. The selectivity of catalyst is dependent on peak 1 of t.d.p. chromatogram. The activity of isomerization is affected by the total acid sites. The activity of dealkylation is increased with an increase of the strength of acid sites. F − added increases the intensity of the (350) reflection and decreases that of (202) Na 2 CO 3 added in synthesis promotes the growth rate of crystal. F − and Na 2 CO 2 added enable mordenite to have different crystal morphology. The activity and selectivity of o -xylene isomerization on HNAM are higher than that on HAM.