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.

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.

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].

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.

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.

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.