Synthesis, Anti-Influenza H1N1 and Anti-Dengue Activity of A-Ring Modified Oleanonic Acid Polyamine Derivatives.

A series of sixteen A-ring modified (2,3-indolo-, 2-benzylidene) oleanonic acid derivatives, holding some cyclic amines, linear polyamines and benzylaminocarboxamides at C28, has been synthesized and screened for antiviral activity against influenza A/PuertoRico/8/34 (H1N1) and Dengue virus serotypes of DENV-1, -2, -3, -4. It was found that 28-homopiperazine 2 and 3-N-phthalyl 22 amides of oleanonic acid demonstrated high potency with selectivity index SI 27 (IC50 21 µM) and 42 (IC50 12 µM). Oleanonic acid aminoethylpiperazine amide 6 and C-azepano-erythrodiol 23 appeared to be the most effective compounds against DENV-1 (IC50's 67 and 107 µM) and -2 (IC50's 86 and 68 µM correspondingly) serotypes.

Potential application of chitosan stabilized silver nanoparticles for simultaneous control of dengue virus and mosquito vectors.

Dengue fever pandemic caused by dengue virus has been claimed for many lives, however, no specific treatment is available. Prevention based on vector control posed to be the most effective measure so far. The application of chitosan stabilized silver nanoparticle (AgNPs) to control larvae and adult mosquitoes has recently discovered, but their ability to inhibit Dengue virus has scarcely discussed. In this study, chitosan stabilized AgNPs have been prepared and tested against dengue virus type 1. The results showed that chitosan stabilized AgNPs can inhibit 96.66% and 98.33% dengue virus type 1 at 12.50 ppm and 25.00 ppm, respectively, without any toxicity to BHKFcɣ cells. This study confirms that chitosan stabilized AgNPs have a highly antiviral ability against dengue virus in addition to its mosquitocidal properties. This allows one to control both virus and vector simultaneously. The study suggested that chitosan stabilized AgNPs could be an effective tool to prevent the dengue epidemic.

Anti-Dengue Screening on Several Vietnamese Medicinal Plants: Experimental Evidences and Computational Analyses.

Worldwide, medicinal plants have been known for economic and geographical advantages, thus possibly holding potentiality against dengue hemorrhagic fever. The methanol/water extracts from different parts of fourteen Vietnam-based plant species were subjected for experimental screening on anti-dengue activity using baby hamster kidney cells (BHK21) and plaque reduction neutralisation test (PRNT). Firstly, the methanol/water extracts were tested against serotype dengue virus DENV-1. Seven out from nineteen extracts show the PRNT50 values less than 31.25 µg/mL. Four of the above extracts namely from Euphorbia hirta, Cordyline terminalis, Carica papaya, and Elaeagnus latifolia were chosen for testing against the serotype DENV-2. All of them exhibit good activity with the PRNT50 values less than 31.25 µg/ml, which were further fractionated to obtain hexane, ethyl acetate and butanol fractions. Anti-dengue virus activity of the fractions against four serotypes DENV-1, -2, -3 and -4 was evaluated. As results, the ethyl acetate fraction of Elaeagnus latifolia is highly active against all four serotype viruses. The structural formulae of its nine constituents were input for molecular docking simulation. The docking-based order for static inhibitability is 6-3L6P>7-3L6P>9-3L6P>2-3L6P>3-3L6P≈5-3L6P>9-3L6P>1-3L6P>8-3L6P; QSARIS-based analysis reveals the biocompatibility of the most promising ligands (4-7); ADMET-based analysis expects their pharmacological suitability. Exceptional finding on 2-3LKW hydrophilic interaction at Lys43 (with the associated Gibbs free energy of -10.3 kcal mol-1 ) raises an open explanation for inhibitory effects. The results encourage further investigations for more in-depth mechanisms and drug development, such as in vitro enzyme assays or in vitro clinical trials with natural substances from E. latifolia.

Alkaloids from Phaeanthus vietnamensis with inhibitory effect on nitric oxide production lipopolysaccharide-stimulated in RAW264.7 macrophages.

The chemical study of the acidic extract of Phaeanthus vietnamensis leaves led to the isolation of one new alkaloid, vietnamine A (1) and eight known alkaloids (R,S)-2N-norberbamunine (2), grisabine (3), 1S,1'R,O,O'-dimethylgrisabine (4), dauricine (5), neothalibrine (6), vietnamine (7), xylopine (8), and argentinine (9) by NMR and MS and comparing with the data reported in the literature. Compounds 1-9 were evaluated for inhibitory NO production in RAW 264.7 macrophages, LPS-stimulated. Compounds 1-3 significantly inhibited on NO production with the IC50 values of 6.8 ± 0.9, 9.8 ± 1.0, and 7.1 ± 0.4 µg/ml, respectively.

Genetic variation in the VP7 gene of rotavirus G1P[8] strains isolated in Vietnam, 1998-2009.

Group A rotavirus genotype G1P[8] is the most common strain affecting humans around the world over the past few decades. In this study, we examined genetic variation in the VP7 gene of rotavirus G1P[8] strains, detected in children of four major cities of Vietnam during three different rotavirus seasons: 1998-1999, 2007-2008 and 2008-2009 in order to assess the evolution of the virus over 11 years. Fecal samples (n=73) from children hospitalized for gastroenteritis caused by G1P[8] rotavirus were analyzed by DNA sequencing of gene 9 encoding the VP7 capsid protein. Phylogenetic analyses indicated that VP7 gene of the G1 strains from 1999 contained a lineage I, while rotaviruses from 2009 clustered in lineage II. Both of these lineages were found co-circulating in 2007-2008 season. While different sublineages of lineage I and II co-circulated in the 1998-1999 and 2007-2008 seasons, almost all strains in 2009 belonged to sub-lineage II-C. In the analysis using selected 10 strains, the VP4 genes of these 2 VP7-G1 lineages were all grouped in F45-like cluster. Deduced amino acid analyses indicated that there were thirteen amino acid substitutions between strains of two lineages. Of those, two were found in antigenic regions A and C, implying possible antigenic differences between these two lineages. The G1P[8] strains in Vietnam are very genetically diverse and dynamic, implying the frequent monitoring on evolution of rotavirus will be important to assess efficacy of rotavirus vaccine in Vietnam.