New nor-lignans from the leaves of styrax annamensis guillaumin.

Phytochemical study of the leaves of Styrax annamensis Guillaumin resulted in the isolation of a new natural product egonol-3''-sulphate (1), and two new derivatives egonol-3-methyl-D-galactopyranoside (2) and 7-methoxy-2-(3',4'-methylenedioxyphenyl)-benzofuran-5-carboxamide (3). Their chemical structures were -elucidated by spectroscopic data. Compounds 1 and 3 significantly established a great role for the chemotaxonomic aspect. Compound 1 showed cytotoxicity against four cancer cell lines KB, HepG2, Lu, and MCF7 with the IC50 values of 84.90-101.69 µg/mL, and exhibited acetylcholinesterase (AChE) inhibitory activity with the IC50 value of 97.08 µg/mL.

Improved synthesis, molecular modeling and anti-inflammatory activity of new fluorinated dihydrofurano-naphthoquinone compounds.

A series of new fluorinated dihydrofurano-napthoquinone compounds were sucessfully synthesized in good yields using microwave-assisted multi-component reactions of 2-hydroxy-1,4-naphthoquinone, fluorinated aromatic aldehydes, and pyridinium bromide. The products were fully characterized using spectroscopic techniques and evaluated for their anti-inflammatory activity using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Among 12 new compounds, compounds 8b, 8d, and 8e showed high potent NO inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells with IC50 values ranging from 1.54 to 3.92 µM. The levels of pro-inflammatory cytokines IL-1ß and IL-6 in LPS-stimulated RAW264.7 macrophages were remarkably decreased after the application of 8b, 8d, 8e and 8k. Molecular docking simulations revealed structure-activity relationships of 8b, 8d, and 8e toward NO synthase, cyclooxygenase (COX-2 over COX-1), and prostaglandin E synthase-1 (mPGES-1). Further physicochemical and pharmacokinetic computations also demonstrated the drug-like characteristics of synthesized compounds. These findings demonstrated the importance of fluorinated dihydrofurano-napthoquinone moieties in the development of potential anti-inflammatory agents.

New Dipterocarpol-Based Molecules with α-Glucosidase Inhibitory and Hypoglycemic Activity.

Dammarane triterpenoids are affordable and bioactive natural metabolites with great structural potential, which makes them attractive sources for drug development. The aim of the study was to investigate the potency of new dipterocarpol derivatives for the treatment of diabetes. Two dammaranes (dipterocarpol and its 20(24)-diene derivative) were modified by a Claisen-Schmidt aldol condensation to afford C2(E)-arylidenes in good yields. The majority of the synthesized compounds exhibited an excellent-to-moderate inhibitory effect toward α-glucosidase (from S. saccharomyces), among them eight compounds showed IC50 values less than 10 µM. 3-Oxo-dammarane-2(E)-benzylidenes (holding p-hydroxy- 3 l and p-carbonyl- 3 m substituents) demonstrated the most potent α-glucosidase inhibition with IC50 0.753 and 0.204 µM, being 232- and 857-times more active than acarbose (IC50 174.90 µM), and a high level of NO inhibition in Raw 264.7 cells with IC50 of 1.75 and 4.57 µM, respectively. An in vivo testing of compound 3 m (in a dose of 20 mg/kg) on a model of streptozotocin-induced T1DM in rats showed a pronounced hypoglycemic activity, the ability to reduce effectively the processes of lipid peroxidation in liver tissue and decrease the excretion of glucose and pyruvic acid in the urine. Compound 3 m reduced the death of diabetic rats and preserved their motor activity.

Twin reversed arterial perfusion sequence-a rare and dangerous complication form of monochorionic twins: A case report.

BACKGROUND: Twin reversed arterial perfusion (TRAP) sequence is an extremely rare congenital anomaly in monochorionic (MC) twins. The condition is characterized by a malformed fetus (acardiac twin) without cardiac activities being perfused by a structurally normal one (pump twin) via an artery-to-artery anastomosis in a reverse direction. CASE SUMMARY: We described the first case of TRAP to receive laser surgery in Vietnam. The 26-wk pregnancy was originally misdiagnosed in another hospital as MC twins with single intrauterine fetal death. Following admission to our center, the diagnosis was amended to a 26-wk TRAP sequence stage IIb. The acardiac twin was 7.5 cm at the longest length, the ratio of the weight of the acardiac twin to the weight of the pump twin was more than 90%, the pump twin showed fetal distress with absent diastolic flow in umbilical artery of pump twin, and the peak systolic velocity in the middle cerebral artery = 1.6 MoM. We performed emergency laser photocoagulation of the acardiac twin's umbilical cord. After surgery, we successfully maintained the pregnancy for 8 wk and ended it electively by cesarean section at 34 wk of gestation due to rupture of membranes. CONCLUSION: TRAP should be appropriately diagnosed and treated early to avoid complications of the pump twin. Fetoscopic laser photocoagulation is a new and effective treatment for this condition.

Microwave-Assisted Three-Component Synthesis of Novel N-Arylated-Dihydrobenzo[g]quinoline-5,10-Diones and Their Potential Cytotoxic Activity.

A convenient three-component synthetic approach was developed en route to new and significative N-arylated-dihydrobenzo[g]quinoline-5,10-diones using 2-hydroxy-1,4-naphthoquinone, a variety of aromatic aldehydes, and 4-(arylamino)furan-2(5H)-ones. A sequence of steps including Knoevenagel condensation, Michael addition, [1,3]-hydrogen shift, intramolecular cyclization and dehydration led to the formation of products. All the products were structurally characterized by spectroscopic techniques and assessed in terms of their cytotoxicity profile against four cancer cell lines (KB, HepG2, A549, and MCF7), and human embryonic kidney (Hek-293) cell lines.

A new cytotoxic compound from the leaves of Styrax annamensis Guillaumin.

New propene derivative 1-(3',4'-methylenedioxyphenyl)-2-(2''-hydroxy-5-(3'''-hydroxypropyl)-3''-methoxyphenyl)prop-2-en-1-one (1), along with three known triterpenoids ursolic acid (2), pomolic acid (3), and maslinic acid (4) were isolated from the leaves of Styrax annamensis species. All structures were assigned by spectroscopic analysis. Compound 1 showed potent cytotoxicity against four cancer cell lines (KB, HepG2, Lu, and MCF7) with the IC50 values of 3.19, 2.87, 2.33, and 2.44 µM, respectively.

Synthesis of messagenin and platanic acid chalcone derivatives and their biological potential.

The chalcone derivatives of 20-oxo-lupanes have been synthesised and screened for some types of biological activity. Ozonolysis of lupanes afforded 20-oxo-derivatives with the following condensation using different aromatic aldehydes by Claisen‒Schmidt reaction to the target compounds. The E configuration of 19-[3-(pyridin-3-yl)-prop-2-en-1-one]-fragment was established by X-ray analysis. Screening of cytotoxic activity against NCI-60 cancer cell line panel revealed, that messagenin derivative 9 has the highest activity with GI50 value ranged from 0.304 to 0.804 µM. A colorimetric SRB assay revealed for the 2,30-bis-furfurylidene derivative 11 and 30-bromo-20-oxo-29-nor-3,28-diacetoxy-betulin 16 cytotoxic activity against breast carcinoma MCF-7 and ovarian carcinoma A2780 cell lines. Compounds 11 and 13 acted also as inhibitors of the enzyme α-glucosidase (from S. saccharomyces) with IC50 values of 1.76 µM and 3.3 µM thus being 97- and 52-fold more active than standard acarbose. Antiviral potency of compounds 12 and 14 against HCMV, HSV-1 and HPV is also discussed.[Formula: see text].

Cytotoxic and α-Glucosidase Inhibitory Xanthones from Garcinia mckeaniana Leaves and Molecular Docking Study.

A new racemic xanthone, garmckeanin A (1), and eight known analogs 2-9 were isolated from the ethyl acetate (AcOEt) extract of the Vietnamese Garcinia mckeaniana leaves. Their structures were determined by MS and NMR spectral analyses and compared with the literature. The AcOEt extract showed good cytotoxicity against cancer cell lines KB, Lu, Hep-G2 and MCF7, with IC50 values of 5.40-8.76 µg/mL, and it also possessed α-glucosidase inhibitory activity, with an IC50 value of 9.17 µg/mL. Garmckeanin A (1) exhibited inhibition of all cancer cell lines, with an IC50 value of 7.3-0.9 µM. Allanxanthone C (5) successfully controlled KB growth, with an IC50 value of 0.54 µM, higher than that of the positive control, ellipticine (IC50 1.22 µM). Norathyriol (8) was a promising α-glucosidase inhibitor, with an IC50 value of 0.07 µM, much higher than that of the positive control, acarbose (IC50 161.0 µM). The interactions of the potential α-glucosidase inhibitors with the C- and N-terminal domains of human intestinal α-glucosidase were also investigated by molecular docking study. The results indicated that bannaxanthone D (2), garcinone E (4), bannaxanthone E (6), and norathyriol (8) exhibit higher binding affinity to the C-terminal than to the N-terminal domain through essential residues in the active sites. In particular, compound 8 could be assumed to be the most potent mixed inhibitor.

New insight into the mechanism of carbon dioxide activation on copper-based catalysts: A theoretical study.

A combination of Artificial Bee Colony algorithm, eXtended Tight Binding and Density functional theory methods were performed to study the activation process of carbon dioxide (CO2) over copper (Cu4 cluster) based catalytic systems. The findings revealed that the activation of the C-O bond resulted from the electron transfer to σ*, π* - MO of CO2. The more the electrons are transferred to CO2, the more the C-O bond is activated and elongated. The suitability of several metal oxide supports (Fe2O3, Al2O3, MgO, ZnO) is estimated using calculated electronic parameters (global electrophilicity index, vertical ionization potential and vertical electron affinity). Aside from demonstrating the appropriateness of Al2O3 and ZnO, a thorough examination of MgO revealed that, due to the formation of stable carbonate products, this oxide is not really appropriate as a support for copper-based catalysts in CO2 conversion. Our studies have also shown that the electron enrichment of copper atoms plays a key role in the activation of C-O bonds. Alkali metal doping (Li, K, Cs) significantly improves the catalytic efficiency of the Cu4 cluster. Based on the results of electron transfer to the CO2 molecule, the effect of doping alkali metal atoms may be organized in the following order: Cs > K > Li. A new core/shell catalytic system with potassium atoms in the core and copper atoms in the shell has been proposed and has proven to be a promising, efficient catalytic system in the CO2 adsorption and activation.

Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma.

Platinum­based antitumor agents have been widely used to treat head and neck squamous cell carcinoma (HNSCC) and numerous other malignancies. Cisplatin is the most frequently used platinum­based antitumor agent, however drug resistance and numerous undesirable side effects limit its clinical efficacy for cancer patients. Cancer cells discharge cisplatin into the extracellular space via copper transporters such as ATPase copper transporting beta (ATP7B) in order to escape from cisplatin­induced cell death. In the present study, it was demonstrated for the first time that the copper chelator ammonium tetrathiomolybdate (TM) has several promising effects on cisplatin and HNSCC. First, TM suppressed the ATP7B expression in HNSCC cell lines in vitro, thereby enhancing the accumulation and apoptotic effect of cisplatin in the cancer cells. Next, it was revealed that TM enhanced the antitumor effect of cisplatin in HNSCC cell tumor progression in a mouse model of bone invasion, which is important since HNSCC cells frequently invade to facial bone. Finally, it was demonstrated that TM was able to overcome the cisplatin resistance of a human cancer cell line, A431, via ATP7B depression in vitro.

Structural modifications of 2,3-indolobetulinic acid: Design and synthesis of highly potent α-glucosidase inhibitors.

A series of nineteen nitrogen-containing lupane triterpenoids was obtained by modification of C2, C3, C20 and C28 positions of betulonic acid and their α-glucosidase inhibiting activity was investigated. Being a leader compound from our previous study, 2,3-indolo-betulinic acid was used as the main template for different modifications at C-(28)-carboxyl group to obtain cyano-, methylcyanoethoxy-, propargyloxy- and carboxamide derivatives. 20-Oxo- and 29-hydroxy-20-oxo-30-nor-analogues of 2,3-indolo-betulinic acid were synthesized by ozonolysis of betulonic acid followed by Fischer indolization reaction. To compare the influence of the fused indole or the seven-membered A-ring on the inhibitory activity, lupane A-azepanones with different substituents at C28 were synthesized. The structure-activity relationships revealed that the enzyme inhibition activity dramatically increased (up to 4730 times) when the carboxylic group of 2,3-indolo-betulinic acid was converted to the corresponding amide. Thus, the IC50 values for glycine amide and L-phenylalanine amides were 0.04 and 0.05 µM, respectively. This study also revealed that 2,3-indolo-platanic acid is 4.5 times more active than the parent triterpenoid with IC50 of 0.4 µM. Molecular modeling suggested that improved potency is due to additional polar interactions formed between C28 side chain and a sub-pocket of the α-glucosidase allosteric site.

Neuromuscular Blockade Agents Reversal with Sugammadex Compared to Neostigmine in the Living Kidney Donors.

BACKROUND: The reversation of NMBA (neuromuscular blocking agents) prevents numerous postoperative complications, increases quality of recovery and decreases the time, expenditure spending in hospital. The choice of medicine used to reverse NMBA depends considered as a key fators to gain the best outcome and to avoid the side effects. AIM: To evaluate the postoperative effect on muscle relaxation reversal and side effects of sugammadex 2 mg/kg versus the combination of neostigmine and atropine sulfate in the living kidney donors. METHODS: A randomised controlled trial on 70 patients undergoing living kidney donation surgery were allocated to 2 groups. Patients in group I (SUGA) were reversed with sugammadex 2 mg/kg and in group II (NEO/ATR) with the combination of neostigmine and atropine sulfat. RESULTS: With 35 patients in each group, the study results showed that after 3 mintutes of reversal patients reaching TOF value ≥ 0.9 in group SUGA is 91.4%, after 5 minutes 100% of patients in group SUGA reached TOF value ≥ 0.9 . In group NEO/ATR after 3 minutes 28.6% patients reached TOF ≥ 0.9 and 40% patients reached TOF≥ 0.9 after 5 minutes. The difference in percentage of patients reaching TOF ≥ 0.9 after 3 minutes, 5 minutes of reversal between two groups is significant (p<0.05). After 10 minutes, 100% patients in both group got TOF ≥ 0.9. Time to exutubation of group SUGA was 249.43 ± 81.75 seconds and it was 456.29 ± 146.45 seconds in group NEO/ATR. Nausea, bradycardia, and increased phlegm production in group NEO/ATR was 22.9%; 28.5%; 25.7% respectively; while those side effects were not met in group SUGA, the difference was significant (p<0.05). CONCLUSION: The muscle relaxation reversal effect of sugammadex was faster than that of neostigmine, the duration TOF ≥ 0.9 and the time to extubation was significantly faster. Sugammadex did not cause hemodynamic changes before and after muscle relaxation reversal, neostigmine resulted in the bradycardia, increased phlegm secreting and other side effects. The renal function after 24 hours postoperatively of two groups was similar.

Synthesis of new simplified hemiasterlin derivatives with α,ß-unsaturated carbonyl moiety.

In this Letter, we report a convenient and efficient method for the synthesis of new simplified derivatives of hemiasterlin in which the α,α-dimethylbenzylic moiety A is replaced by α,ß-unsaturated aryl groups as Michael acceptor. Most of these derivatives have a strong cytotoxic activity on three human tumor cell lines (KB, Hep-G2 and MCF7). Analogs 17b and 17f showed a high cytotoxicity against KB and Hep-G2 cancer cell lines comparable to paclitaxel and ellipticine.

Prevention and control of fish-borne zoonotic trematodes in fish nurseries, Vietnam.

Worldwide, >18 million persons were infected with fish-borne zoonotic trematodes in 2002. To evaluate the effectiveness of interventions for reducing prevalence and intensity of fish-borne zoonotic trematode infections in juvenile fish, we compared transmission rates at nurseries in the Red River Delta, northern Vietnam. Rates were significantly lower for nurseries that reduced snail populations and trematode egg contamination in ponds than for nurseries that did not. These interventions can be used in the development of programs for sustained control of zoonotic trematodes in farmed fish.

Radon ((222)Rn) concentration in indoor air near the coal mining area of Nui Beo, North of Vietnam.

Concentrations of radioactive radon gas ((222)Rn) were measured using passive monitors based on LR115 solid state track detectors during June-July 2010 in indoor air of dwellings in the Nui Beo coal mining area, mostly in Cam Pha and Ha Long coastal towns, Quang Ninh province, in the North of Vietnam. Global results of (222)Rn concentrations indoors varied from ≤6 to 145 Bq m(-3) averaging 46 ± 26 Bq m(-3) (n = 37), with a median value of 47 Bq m(-3). This was similar to outdoor (222)Rn concentrations in the region, averaging 43 ± 19 Bq m(-3) (n = 10), with a median value of 44 Bq m(-3). Indoor (222)Rn concentrations in the coastal town dwellings only were in average lower although not significantly different from indoor (222)Rn concentrations measured at the coal storage field near the harbor, 67 ± 4 Bq m(-3) (n = 3). Furthermore, there was no significant difference in the average (222)Rn concentration in indoor air measured in the coastal towns region and those at the touristic Tuan Chau Island located about 45 km south of the coal mine, in the Ha Long Bay. The indoor (222)Rn concentration in a floating house at the Bai Tu Long Bay, and assumed as the best estimate of the baseline (222)Rn in surface air, was 27 ± 3 Bq m(-3) (n = 3). Indoor average concentration of (222)Rn in dwellings at the Ha Noi city, inland and outside the coal mining area, was determined at 30 Bq m(-3). These results suggest that (222)Rn exhalation from the ground at the Nui Beo coal mining area may have contributed to generally increase (222)Rn concentration in the surface air of that region up to 1.7 times above the baseline value measured at the Bai Tu Long Bay and Ha Noi. The average indoor concentration of (222)Rn in Cam Pha-Ha Long area is about one-third of the value of the so-called Action Level set up by the US EPA of 148 Bq m(-3). Results suggest that there is no significant public health risk from (222)Rn exposure in the study region.

The presence of high level soluble herpes virus entry mediator in sera of gastric cancer patients

The development of gastric cancer (GC) is closely related to chronic inflammation caused by Helicobacter pylori infection, and herpes virus entry mediator (HVEM) is a receptor expressed on the surface of leukocytes that mediates potent inflammatory responses in animal models. However, the role of HVEM in human GC has not been studied. Previously, we showed that the interaction of HVEM on human leukocytes with its ligand LIGHT induces intracellular calcium mobilization, which results in inflammatory responses including induction of proinflammatory cytokine production and anti-bacterial activities. In this study, we report that leukocytes from GC patients express lower levels of membrane HVEM (mHVEM) and have lower LIGHT-induced bactericidal activities than those from healthy controls (HC). In contrast, levels of soluble HVEM (sHVEM) in the sera of GC patients were significantly higher than in those of HC. We found that monocyte membrane-bound HVEM is released into the medium when cells are activated by proinflammatory cytokines such as TNF-alpha and IL-8, which are elevated in the sera of GC patients. mHVEM level dropped in parallel with the release of sHVEM, and release was completely blocked by the metalloprotease inhibitor, GM6001. We also found that the low level of mHVEM on GC patient leukocytes was correlated with low LIGHT-induced bactericidal activities against H. pylori and S. aureus and production of reactive oxygen species. Our results indicate that mHVEM on leukocytes and sHVEM in sera may contribute to the development and/or progression of GC.