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It is urgently necessary to develop more effective anti-influenza agents due to the continuous emergence of drug-resistant strains of influenza virus. Our earlier studies have identified that certain pentacyclic triterpene derivatives are effective inhibitors of influenza virus infection. In the present study, a series of C-28 modified pentacyclic triterpene derivatives via conjugation with a series of polyphenols were synthesized, and their antiviral activities against influenza A/WSN/33 (H1N1) virus in MDCK (Madin-Darby canine kidney) cells were evaluated. Four compounds 23m, 23o, 23q and 23s displayed robust anti-influenza potency with averaged IC50 values at the low-micromole level, surpassing the potency of oseltamivir. In addition, the in vitro cytotoxic activity of the four conjugates against MDCK cells showed no toxicity at 100 μM. Further mechanism studies of compound 23s, one of the best representative conjugates with IC50 value of 5.80 μM and a selective index (SI) value of over 17.2, by hemagglutination inhibition (HI), surface plasmon resonance and molecular modeling indicated that this conjugate bound tightly to the viral envelope hemagglutinin (KD = 15.6 μM), thus blocking the invasion of influenza viruses into host cells.

Titanium dioxide (TiO2) aerogels were prepared with sol–gel ambient pressure drying method by using titanium tetrachloride (TiCl4) as precursor and tetraethoxysilane as modifier, calcinated at different temperature and characterized by X-ray diffraction, transmission electron microscopy and small angle X-ray scattering. The results showed that the TiO2 aerogels remained amorphous under 500 °C, changed to anatase from 600 °C and further changed to rutile from 900 °C. Between 60 °C and 500 °C, the primary particles within the samples concentrated mainly upon small sizes, enlarged and diverged remarkably above 600 °C. The crystalline grains grew and agglomerated with the rise of the calcination temperature. The TiO2 aerogels at a temperature higher than 800 °C have better stability than anatase because of the formation of partial Ti―O―Si bonds. Copyright © 2016 John Wiley & Sons, Ltd.

Oleanolic acid (OA) and echinocystic acid (EA), two naturally occurring pentacyclic oleanane triterpenes, are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic α(β)-cyclodextrin (CD) via “click chemistry” can improve their solubility and anti-HCV entry potency. In the present work, four water-soluble β-CD-pentacyclic triterpene conjugates were designed and synthesized, in which OA and EA was coupled to one of the primary hydroxyl groups of β-CD via ester and amide bonds. The structures of the conjugates were unambiguously determined by 1H NMR, 13C NMR and HRMS or MALDI-TOF-MS. All the conjugates showed lower hydrophobicity (AlogP) than their parent compounds and no significant cytotoxicity was found to HL-60, A549, Hela and Bel-7402 cells at concentrations up to 10 μmol/L. Further anti-HCV entry activity and mechanism studies are under way in our laboratory.

Sialic acid derivatives, analogs, and their conjugates are important pharmacophores. Modification of the C-4 hydroxyl group of sialic acid can lead to derivatives, such as zanamivir, with potent anti-influenza activities. Herein, we described the synthesis of C-4-modified sialic acid derivatives

A series of novel tetrazole containing 1,2,3-thiadiazole derivatives were designed and synthesized via Ugi reaction. Their structures were confirmed by melting points, IR, 1H NMR, and HRMS (ESI). Preliminary bioassay indicated that most target compounds exhibited very good direct anti-TMV activity at 100 μg/mL, which was equal to or higher than that of ribavirin. Among them, compounds 4b, 4c and 4i also showed equivalent protection effect to ribavirin in vivo at 100 μg/mL. © 2013 Zhi-Jin Fan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Some tricyclohexyltin(IV) carboxylates, HOOC–R–COOSn(c-C6H11)3 (1) and (c-C6H11)3SnOOC–R–COOSn(c-C6H11)3 (2) [R = 1,2-C6H4 (a), 1,2-C6F4 (b), (Z)-CH=CH (c), CH2CH2 (d)], have been synthesized from reaction of tricyclohexyltin hydroxide with cyclic dicarboxylic anhydrides under microwave irradiation in 1 : 1 and 2 : 1 M ratio, respectively, and characterized by elemental analysis, IR and NMR (1H, 13C, and 119Sn) spectra. Crystal structures of 1a–1c and 2d are determined by X-ray single crystal diffraction. The carboxylate in each compound is monodentate to tin. Compounds 1a and 1c possess a trans-C3SnO2 trigonal bipyramidal geometry with axial positions occupied by carboxylate and carbonyl oxygen of carboxylate of an adjacent molecule forming a one-dimensional chain. Compound 1b is tetrahedral and forms R 2 2(8) hydrogen-bonded dimers by pairs of intermolecular O–H O hydrogen bonds between two carboxylic acid groups. Compound 2d is dinuclear with tin possessing distorted tetrahedral geometry; a trimer supr...

The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold more potent antiviral activity was observed when sialic acid was conjugated with pentacyclic triterpene via C-4 than C-2. It was here that we further reported the synthesis and anti-influenza activity of novel sialic acid (C-5 and C-9)-pentacyclic triterpene conjugates. Their structures were confirmed by ESI-HRMS, 1H-NMR, and 13C-NMR spectroscopic analyses. Two conjugates (26 and 42) showed strong cytotoxicity to MDCK cells in the CellTiter-Glo assay at a concentration of 100 μM. However, they showed no significant cytotoxicity to HL-60, Hela, and A549 cell lines in MTT assay under the concentration of 10 μM (except compound 42 showed weak cytotoxicity to HL-60 cell line (10 μM, ~53%)). Compounds 20, 28, 36, and 44 displayed weak potency to influenza A/WSN/33 (H1N1) virus (100 μM, ~20–30%), and no significant anti-influenza activity was found for the other conjugates. The data suggested that both the C-5 acetylamide and C-9 hydroxy of sialic acid were important for its binding with hemagglutinin during viral entry into host cells, while C-4 and C-2 hydroxy were not critical for the binding process and could be replaced with hydrophobic moieties. The research presented herein had significant implications for the design of novel antiviral inhibitors based on a sialic acid scaffold.

Sialic acid derivatives, analogs, and their conjugates are important pharmacophores. Modification of the C-4 hydroxyl group of sialic acid can lead to derivatives, such as zanamivir, with potent anti-influenza activities. Herein, we described the synthesis of C-4-modified sialic acid derivatives via conjugation with naturally derived pentacyclic triterpenes, which are active ingredients of traditional Chinese medicine, and the evaluation of their in vitro anti-influenza virus activity in MDCK cells. Interestingly, a set of configurational isomers was obtained during the de-O-acetylation reaction of two pentacyclic triterpene-sialic acid conjugates under Zemplen conditions, and a mechanism was proposed. Owing to the attachment of the Neu5Ac2en moiety, all synthesized conjugates displayed lower hydrophobicity than their parent compounds. In comparison with ursane- and lupane-type triterpenes, oleanane-type triterpene-functionalized Neu5Ac2en conjugates were most promising. The insertion of a (1,2,3-triazol-4-yl)-methyl between the amide bond and Neu5Ac2en caused a substantial decrease in activity. Compound 15a exhibited the highest inhibitory activity (IC50 = 8.3 μM) and selectivity index (SI = 22.7). Further studies involving hemagglutination inhibition and neuraminidase inhibition suggested that compound 15a inhibited virus-induced hemagglutination with no effect on the enzymatic activity of neuraminidase, indicating that the antiviral activity appeared to be mediated via interaction with hemagglutinin at the initial stage of viral infection.

The title compounds, quinolin-8-yl 4-methyl-1,2,3-thiadiazole-5-carboxylate 2a and 2-nitrophenyl 4-methyl-1,2,3-thiadiazole-5-carboxylate 2b, synthesized by the reaction of 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride with 8-hydroxyquinoline and 2-nitrophenol, were confirmed by single-crystal X-ray diffraction [CCDC 783328 and 784970]. The 2a crystallizes in triclinic space group P-1 with cell parameters a = 7.957(7) A, b = 8.378(7) A, c = 10.097(10) A, α = 100.63(2)°, β = 112.742(17)°, γ = 93.287(4)° and Z = 2. The 2b crystallizes in triclinic space group P-1 with cell parameters a = 7.134(4) A, b = 8.154(4) A, c = 10.254(5) A, α = 99.501(9)°, β = 91.311(7)°, γ = 109.518(8)° and Z = 2. Packing in the compound 2a is dominated by weak C–H···N and C–H···O hydrogen bonds. In the compound 2b, molecules are linked through intermolecular C–H···O hydrogen bonds interactions. The preliminary bioassay showed that the title compound 2a had excellent antifungal activity with the EC50 detected as from 2.99 to 28.35 μg/mL and the EC90 detected as from 21.041 to 175.17 μg/mL. Both of the title compounds 2a and 2b had good inhibition activity of tobacco mosaic virus (TMV) and good induction activity of tobacco against TMV with potential systemic acquired resistance. Two 1,2,3-thiadiazole derivatives C13H9N3O2S (2a) and C10H7N3O4S (2b), synthesized by the reaction of 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride with 8-hydroxyquinoline and 2-nitrophenol, were confirmed by single-crystal X-ray diffraction. The preliminary bioassay shows that the title compound 2a has excellent antifungal activity. Both of the title compounds 2a and 2b had good inhibition activity of tobacco mosaic virus (TMV) and good induction activity of tobacco against TMV with potential systemic acquired resistance.

In the experimental advanced superconducting tokamak, density pump-out phenomena were observed by using a multi-channel polarimeter-interferometer system under different heating schemes of ion cyclotron resonant heating, electron cyclotron resonance heating, and neutral beam injection. The density pump-out was also induced with application of resonant magnetic perturbation, accompanied with a degradation of particle confinement. For the comparison analysis in all heating schemes, the typical plasma parameters are plasma current 400 kA, toroidal field 2 T, and line average density 2 × 1019 m−3. The experimental results show that the degree of pump-out is concerned with electron density and heating power. Low density deuterium low confinement (L-mode) plasmas (

Compounds (Vh) and (Vj) show considerable larvicidal activity against Culex pipiens pallens.