Fate of endosulfan in ginseng farm and effect of granular biochar treatment on endosulfan accumulation in ginseng.

Endosulfan was widely used as an insecticide in the agricultural sector before its environmental persistence was fully understood. Although its fate and transport in the environment have been studied, the effects of historic endosulfan residues in soil and its bioaccumulation in crops are not well understood. This knowledge gap was addressed by investigating the dissipation and bioaccumulation of endosulfan in ginseng as a perennial crop in fresh and aged endosulfan-contaminated fields. In addition, the effect of granular biochar (GBC) treatment on the bioaccumulation factor (BAF) of endosulfan residue in ginseng was assessed. The 50% dissipation time (DT50) of the total endosulfan was over 770 days in both the fresh and aged soils under mulching conditions. This was at least twofold greater than the reported (6- > 200 days) in arable soil. Among the endosulfan congeners, the main contributor to the soil residue was endosulfan sulfate, as observed from 150 days after treatment. The BAF for the 2-year-old ginseng was similar in the fresh (1.682-2.055) and aged (1.372-2.570) soils, whereas the BAF for the 3-year-old ginseng in the aged soil (1.087-1.137) was lower than that in the fresh soil (1.771-2.387). The treatment with 0.3 wt% GBC extended the DT50 of endosulfan in soil; however, this could successfully suppress endosulfan uptake, and reduced the BAFs by 66.5-67.7% in the freshly contaminated soil and 32.3-41.4% in the aged soil. Thus, this adsorbent treatment could be an effective, financially viable, and sustainable option to protect human health by reducing plant uptake of endosulfan from contaminated soils.

Effect of soil organic matter on the plant uptake of perfluorooctanoic acid (PFOA) and perfluorooctanesulphonic acid (PFOS) in lettuce on granular activated carbon-applied soil.

The presence of perfluorooctanoic acid (PFOA) and perfluorooctanesulphonic acid (PFOS) in crops is an important consideration for food safety. The soil organic matter (SOM) content may affect the adsorption potential of PFOA and PFOS in water and soil and their subsequent uptake in crops. To better understand these dynamics, the adsorption and uptake of PFOA and PFOS in lettuce were investigated using granular activated carbon (GAC)-treated soils with varying SOM content. The adsorption potential of GAC was investigated, with maximum adsorption capacities for PFOA and PFOS calculated to be 9.091 mg g-1 and 27.778 mg g-1, respectively. These values decreased to 5.208 mg g-1 and 17.241 mg g-1, respectively, after the addition of 0.04 wt% humic acid. The average plant uptake factor (PUF) in low and high perfluoroalkyl and polyfluoroalkyl acid (PFAA)-contaminated soils with 4.0 wt% SOM was restricted to 0.353 for PFOA and 0.108 for PFOS. The PUFs were approximately two times lower than those for soil with 2.6 wt% SOM. Addition of 1 wt% GAC to the soil successfully reduced the PUF by up to 99.4%, with values of 0.006 (PFOA) and 0.005 (PFOS) in 2.6 wt% SOM-treated soil and 0.079 (PFOA) and 0.023 (PFOS) in 4.0 wt% SOM-treated soil. Although the PUF in the GAC-treated soil was drastically decreased, the PUF of the soil with 4.0 wt% SOM was at least four times higher than that with 2.6 wt% SOM. Therefore, SOM content is an important consideration in the remediation of PFOA- and PFOS-contaminated farmland soil using carbonaceous adsorbent.

Environmental and dietary exposure of perfluorooctanoic acid and perfluorooctanesulfonic acid in the Nakdong River, Korea.

This study performed the first environmental and dietary exposure assessment to explore plant uptake of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) from agricultural soil and irrigation water in the Nakdong River delta, South Korea. Annual average concentrations of total PFOA and PFOS ranged from 0.026 to 0.112 µg L-1 (irrigation water), and from 0.818 to 1.364 µg kg-1 (soil), respectively. PFOA and PFOS hotspots were identified downstream of the Nakdong River and were influenced by seasonal climatic variations. The observed average biennial concentration of the sum of PFOA and PFOS decreased in irrigation water, from 0.112 µg L-1 in 2013 to 0.026 µg L-1 in 2015, suggests that the 2013 Persistent Organic Pollutants Control Act may have helped to reduce levels of PFAS at this location. This study calculated some of the highest plant uptake factors reported to date, with values ranging from 0.962 in green onions to < 0.004 in plums. Leafy vegetables and rice are important components of the Korean diet; these groups had the largest contribution to the estimated dietary intake of PFOA and PFOS, which was calculated at 0.449 and 0.140 ng kg bw -1 day-1, respectively. This corresponded to 66.4% for PFOA and 7.9% for PFOS of the EFSA reference dose (RfD). The dietary intake of PFOA and PFOS from crops alone did not exceed the RfD. However, when the estimated daily intake (EDI) from other sources such as tap water, meat, fish, dairy, and beverages was included in the exposure risk assessment, both of the EDIs to PFOA and PFOS exceeded the RfDs, indicating that there may be a risk to human health. This study concludes that consumption of crops might, therefore, be a significant and underappreciated pathway for human exposure to PFAS.

Per- and Polyfluoroalkyl Substances in the Air Particles of Asia: Levels, Seasonality, and Size-Dependent Distribution.

Information regarding the size-dependent distribution of per- and polyfluoroalkyl substances (PFAS) in atmospheric particulate matter (PM) is very limited. In this study, 248 size-specific PM samples were collected from 9 Asian cities using a portable 4-stage cascade impactor for the analysis of PFAS. Of the 34 investigated PFAS, perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) were the major compounds. In particular, the emerging PFAS, hexafluoropropylene oxide dimer acid, was quantified in the PM for the first time, with concentrations ranging from <0.086 to 21.5 pg/m3. Spatially, PFOA and PFOS were the predominant compounds in China, while precursors, emerging PFAS, and short-chain PFAS dominated in India, Japan, and South Korea, respectively. Seasonal variations of PFAS may be controlled by regional climate, local or seasonal emission sources, and long-range transport of air masses. Size-dependent distribution was investigated, showing that the majority of PFAS predominantly affiliated in fine particles, while PFOS and its alternatives tended to attach on coarser particles. Moreover, PFOS distributed on specific sizes exhibited seasonal and regional dependency, while no such patterns were observed for PFOA. These findings will provide useful information on the geographical and size-dependent distribution of PFAS in the atmospheric PM.

Phenylephrine, a small molecule, inhibits pectin methylesterases.

Pectin methylesterases (PMEs) catalyze pectin demethylation and facilitate the determination of the degree of methyl esterification of cell wall in higher plants. The regulation of PME activity through endogenous proteinaceous PME inhibitors (PMEIs) alters the status of pectin methylation and influences plant growth and development. In this study, we performed a PMEI screening assay using a chemical library and identified a strong inhibitor, phenylephrine (PE). PE, a small molecule, competitively inhibited plant PMEs, including orange PME and Arabidopsis PME. Physiologically, cultivation of Brassica campestris seedlings in the presence of PE showed root growth inhibition. Microscopic observation revealed that PE inhibits elongation and development of root hairs. Molecular studies demonstrated that Root Hair Specific 12 (RHS12) encoding a PME, which plays a role in root hair development, was inhibited by PE with a Ki value of 44.1 µM. The biochemical mechanism of PE-mediated PME inhibition as well as a molecular docking model between PE and RHS12 revealed that PE interacts within the catalytic cleft of RHS12 and interferes with PME catalytic activity. Taken together, these findings suggest that PE is a novel and non-proteinaceous PME inhibitor. Furthermore, PE could be a lead compound for developing a potent plant growth regulator in agriculture.

Phytotoxic mechanisms of bur cucumber seed extracts on lettuce with special reference to analysis of chloroplast proteins, phytohormones, and nutritional elements.

Bioherbicides from plant extracts are an effective and environmentally friendly method to prevent weed growth. The present investigation was aimed at determining the inhibitory effect of bur cucumber seed extracts (BSE) on lettuce plant growth. Bur cucumber seeds were ground with water, and two different concentrations of seed extracts (10% and 20%) were prepared and applied to lettuce plants. Decreased plant height, number of leaves, leaf length, leaf width, anProd. Type: FTPd leaf area were found in lettuce exposed to BSE as compared with controls. A significant reduction in lettuce biomass was observed in 20% BSE-treated plants due to the presence of higher amounts of phenolic content in the extracts. Moreover, a significant inhibitory chemical, 2-linoleoyl glycerol, was identified in BSE extracts. The mechanism of plant growth inhibition was assayed in lettuce proteins by 2-dimensional electrophoresis (2-DE) and the LC-MS/MS method. In total, 57 protein spots were detected in plants treated with 20% BSE and control plants. Among these, 39 proteins were down-regulated and 18 proteins were up-regulated in plants exposed to 20% BSE as compared with controls. The presence of low levels of chlorophyll a/b binding protein and oxygen-evolving enhancer protein 1 in BSE-exposed plants reduced photosynthetic pigment synthesis and might be a reason for stunted plant growth. Indeed, the plant-growth stimulating hormone gibberellin was inhibited, and synthesis of stress hormones such as abscisic acid, jasmonic acid, and salicylic acid were triggered in lettuce by the effects of BSE. Uptake of essential nutrients, Ca, Fe, Mg, K, S, and Mo, was deficient and accumulation of the toxic ions Cu, Zn, and Na was higher in BSE-treated plants. The results of this study suggest that extracts of bur cucumber seeds can be an effective eco-friendly bioherbicide for weed control that work by inhibiting mechanisms of photosynthesis and regulating phytohormones and nutritional elements.

Mangosenone F, A Furanoxanthone from Garciana mangostana, Induces Reactive Oxygen Species-Mediated Apoptosis in Lung Cancer Cells and Decreases Xenograft Tumor Growth.

Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI-H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bax, suggesting that caspase-mediated pathways were involved in MSF-induced apoptosis. ROS activation of the mitogen-activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI-H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production.

Multiple Leader Candidate and Competitive Position Allocation for Robust Formation against Member Robot Faults.

This paper proposes a Multiple Leader Candidate (MLC) structure and a Competitive Position Allocation (CPA) algorithm which can be applicable for various applications including environmental sensing. Unlike previous formation structures such as virtual-leader and actual-leader structures with position allocation including a rigid allocation and an optimization based allocation, the formation employing the proposed MLC structure and CPA algorithm is robust against the fault (or disappearance) of the member robots and reduces the entire cost. In the MLC structure, a leader of the entire system is chosen among leader candidate robots. The CPA algorithm is the decentralized position allocation algorithm that assigns the robots to the vertex of the formation via the competition of the adjacent robots. The numerical simulations and experimental results are included to show the feasibility and the performance of the multiple robot system employing the proposed MLC structure and the CPA algorithm.

Structural and biochemical characterization of the broad substrate specificity of Bacteroides thetaiotaomicron commensal sialidase.

Sialidases release the terminal sialic acid residue from a wide range of sialic acid-containing polysaccharides. Bacteroides thetaiotaomicron, a symbiotic commensal microbe, resides in and dominates the human intestinal tract. We characterized the recombinant sialidase from B. thetaiotaomicron (BTSA) and demonstrated that it has broad substrate specificity with a relative activity of 97, 100 and 64 for 2,3-, 2,6- and 2,8-linked sialic substrates, respectively. The hydrolysis activity of BTSA was inhibited by a transition state analogue, 2-deoxy-2,3-dehydro-N-acetyl neuraminic acid, by competitive inhibition with a Ki value of 35µM. The structure of BSTA was determined at a resolution of 2.3Å. This structure exhibited a unique carbohydrate-binding domain (CBM) at its N-terminus (a.a. 23-190) that is adjacent to the catalytic domain (a.a. 191-535). The catalytic domain has a conserved arginine triad with a wide-open entrance for the substrate that exposes the catalytic residue to the surface. Unlike other pathogenic sialidases, the polysaccharide-binding site in the CBM is near the active site and possibly holds and positions the polysaccharide substrate directly at the active site. The structural feature of a wide substrate-binding groove and closer proximity of the polysaccharide-binding site to the active site could be a unique signature of the commensal sialidase BTSA and provide a molecular basis for its pharmaceutical application.

Tuning mechanism-based inactivators of neuraminidases: mechanistic and structural insights.

3-Fluorosialosyl fluorides are inhibitors of sialidases that function by the formation of a long-lived covalent active-site adduct and have potential as therapeutics if made specific for the pathogen sialidase. Surprisingly, human Neu2 and the Trypanosoma cruzi trans-sialidase are inactivated more rapidly by the reagent with an equatorial fluorine at C3 than by its axial epimer, with reactivation following the same pattern. To explore a possible stereoelectronic basis for this, rate constants for spontaneous hydrolysis of the full series of four 3-fluorosialosyl fluorides were measured, and ground-state energies for each computed. The alpha (equatorial) anomeric fluorides hydrolyze more rapidly than their beta anomers, consistent with their higher ground-state energies. However ground-state energies do not explain the relative spontaneous reactivities of the 3-fluoro-epimers. The three-dimensional structures of the two 3-fluoro-sialosyl enzyme intermediates of human Neu2 were solved, revealing key stabilizing interactions between Arg21 and the equatorial, but not the axial, fluorine. Because of changes in geometry these interactions will increase at the transition state, likely explaining the difference in reaction rates.

Effect of Abiotic Signals on the Accumulation of Saponarin in Barley Leaves in Hydroponics Under Artificial Lights.

Functional flavonoid production is a new agenda in the agricultural industry, and young barley leaves (YBL) are one of the highlighted crops due to their health-beneficial flavonoid, saponarin. For the year-round cultivation of a high saponarin content of YBL, abiotic signal effects on the biosynthesis and metabolism in YBL need to be understood clearly. In this research, the effects of reactive oxygen species (ROS)-related abiotic signals, such as light, potassium, and sodium, were investigated on the biosynthetic metabolism in YBL cultivation under artificial lights. A higher quantity of blue-rich white light (6500 K of light temperature) irradiation enhanced ROS levels and the related enzyme activities (APX and CAT), as well as photosynthesis and saponarin amount, while red-rich white light (3000 K of light temperature) increased the photosynthesis only. In addition, 1.0 g L-1 K+ treatment in water slightly reduced ROS levels and increased saponarin accumulation in YBL. These blue-rich light and K+ supplemental conditions relatively increased OGT expression and reduced 4-coumaric acid and isovitexin as saponarin precursors. Furthermore, the relative ratio of lutonarin as an oxidized product of saponarin increased in increments of light quantity. Finally, the abiotic conditions for saponarin production were optimized with the mixture solution treatment of 1.0 g L-1 Na+ and 1.0 g L-1 K+ under 500 PPFD of 6500 K light, and the saponarin amount per leaf was 219.5 µg plant-1; it was comparable amount with that under sunlight condition.

The association between occupational stress level and health-related productivity loss among Korean employees.

OBJECTIVES: Occupational stress management is particularly important for successful business operations, since occupational stress adversely affects workers' health, eventually lowering their productivity. Therefore, this study aimed to investigate the correlation between occupational stress and health-related productivity loss (HRPL) among Korean workers. METHODS: In 2021, 1,078 workers participated in a web-based questionnaire survey. HRPL was measured using the Work Productivity and Activity Impairment Questionnaire, and occupational stress was measured using the Korean Occupational Stress Scale-Short Form. The occupational stress level was divided into tertiles (low, intermediate, and high), and the low occupational stress group was used as the reference group. Using a generalised linear model, differences in labour productivity loss according to the level of occupational stress were tested after adjusting for demographic characteristics such as age, gender, education level, household income, occupation, and underlying medical conditions. RESULTS: Non-parametric regression analysis of HRPL according to occupational stress showed a direct association between occupational stress and HRPL. A statistically significant difference was observed in HRPL between participants with intermediate and high occupational stress and those with low occupational stress. CONCLUSIONS: Our results support the hypothesis that high occupational stress is associated with decreased labour productivity.

Comparative Bioactivity of Emamectin Benzoate Formulations against the Pine Wood Nematode, Bursaphelenchus xylophilus.

The pine wood nematode (PWN), Bursaphelenchus xylophilus is a well-known devastating pathogen of economic importance in the Republic of Korea and other countries. In the Republic of Korea, trunk injection of nematicides is the preferred method of control. In this study, the efficacy of 16 locally produced formulations of emamectin benzoate against the PWN are compared through determining their sublethal toxicities and reproduction inhibition potentials. Nematodes were treated with varying concentrations of the tested chemicals in multi-well culture plates, and rates of paralysis and mortality were determined after 24 h. Reproduction inhibition potential was tested by inoculating pre-treated nematodes onto Botrytis cinerea, and in pine twig cuttings. Despite the uniformity in the concentration of the active ingredient, efficacy was contrastingly different among formulations. The formulations evidently conformed to three distinct groups based on similarities in sublethal activity (group 1: LC95 of 0.00768-0.01443 mg/ml; group 2: LC95 of 0.03202-0.07236 mg/ml, and group 3: LC95 of as high as 0.30643-0.40811 mg/ml). Nematode paralysis generally occurred at the application dose of 0.0134-0.1075 µg/ml, and there were significant differences in nematode paralysis rates among the products. Nematode reproduction was only evident at lower doses both on B. cinerea and pine twigs, albeit the variations among formulations. Group 1 formulations significantly reduced nematode reproduction even at a lower dose of 0.001075 µg/ml. The variations in efficacy might be attributed to differences in inert ingredients. Therefore, there is need to analyze the potential antagonistic effects of the large number of additives used in formulations.

Photochemical advanced oxidative process treatment effect on the pesticide residues reduction and quality changes in dried red peppers.

Pesticide residues in crops are widely monitored, and the residue reduction techniques at the post-harvest stage are important to maintain food safety. In dried crops, pesticide residues can be concentrated after dehydration, which increases concerns regarding residue risk. Therefore, the residue reduction effects of ultraviolet (UV), ozone, and photochemical advanced oxidative process (pAOP) were investigated for dried peppers at the post-harvest stage. UV254 treatment reduced 59.7% of the residue concentration on average, while UV360 showed a reduction of only 13.3% under 9.6 W m-2 of UV exposure for 24 h. Gaseous ozone treatments reduced the residue concentrations up to 57.9% on average. In contrast, the pAOP treatment reduced the concentration up to 97% and was superior to UV or ozone treatment alone. Increased drying temperature under pAOP condition resulted in higher reduction ratios at 40-80 °C. The pAOP conditions with 12 and 24 µmol/mol of ozone and UV254 irradiation for 24-48 h reduced the residue concentrations to 39-67%. Particularly, difenoconazole, fludioxonil, imidacloprid, and thiamethoxam residue concentrations were drastically reduced by over 50% under 12 µmol/mol ozone of the pAOP condition, while carbendazim, fluquinconazole, and pyrimethanil were relatively stable and their concentrations reduced below 50% under 24 µmol/mol ozone of the pAOP treatment. Various drying-related quality parameters of drying peppers such as water-soluble color, capsanthin, capsaicinoids, acid value, peroxide value, and thiobarbituric acid value were slightly altered, but not significantly, under 12 µmol/mol ozone of the pAOP condition, while the peroxide value was significantly altered under the higher ozone conditions. Therefore, pAOP treatment combined with gaseous ozone can be used for reducing residual pesticides in peppers without greatly reducing quality.

The Potency of Abamectin Formulations against the Pine Wood Nematode, Bursaphelenchus xylophilus.

Abamectin offers great protection against Bursaphelenchus xylophilus, a well-known devastating pathogen of pine tree stands. Trunk injection of nematicides is currently the most preferred method of control. This study aimed to evaluate the potency of the commonly used formulations of abamectin against B. xylophilus. Twenty-one formulations of abamectin were evaluated by comparing their sublethal toxicities and reproduction inhibition potentials against B. xylophilus. Nematodes were treated with diluted formulation concentrations in multi-well culture plates. And, populations pre-exposed to pre-determined concentrations of the formulations were inoculated onto Botrytis cinerea culture, and in pine twig cuttings. Potency was contrastingly different among formulations, with LC95 of 0.00285 and 0.39462 mg/ml for the most, and the least potent formulation, respectively. Paralysis generally occurred at an application dose of 0.06 µg/ml or higher, and formulations with high sublethal toxicities caused significant paralysis levels at the tested doses, albeit the variations. Nematode reproduction was evident at lower doses of 0.00053-0.0006 µg/ml both on Botrytis cinerea and pine twigs, with significant variations among formulations. Thus, the study highlighted the inconsistencies in the potency of similar product formulations with the same active ingredient concentration against the target organism, and the need to analyze the potential antagonistic effects of the additives used in formulations.

Inhibitory evaluation of sulfonamide chalcones on β-secretase and acylcholinesterase.

The action of ß-secretase (BACE1) is strongly correlated with the onset of Alzheimer's disease (AD). Aminochalcone derivatives were examined for their ability to inhibit BACE1. Parent aminochalcones showed two digit micromolar IC(50)s against BACE1. Potency was enhanced 10-fold or more by introducing benzenesulfonyl derivatives to the amino group: 1 (IC(50) = 48.2 µM) versus 4a (IC(50) = 1.44 µM) and 2 (IC(50) = 17.7 µM) versus 5a (IC(50) = 0.21 µM). The activity was significantly influenced by position and number of hydroxyl groups on the chalcone B-ring: 3,4-dihydroxy 5a (IC(50) = 0.21 µM) > 4-hydroxy 4a (IC(50) = 1.44 µM) > 2,4-dihydroxy 6 (IC(50) = 3.60 µM) > 2,5-dihydroxy 7 (IC(50) = 16.87 µM) > des hydroxy 4b (IC(50) = 168.7 µM). Lineweaver-Burk and Dixon plots and their secondary replots indicate that compound 5a was a mixed inhibitor with reversible and time-dependent behavior. Potent BACE1 inhibitors 4a,c,f, 5a-c showed moderate inhibition against two other enzymes implicated in AD pathogenesis, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with IC(50)s ranging between 56.1 ~ 95.8 µM and 19.5 ~ 79.0 µM, respectively.

A comparison of the effectiveness of QuEChERS, FaPEx and a modified QuEChERS method on the determination of organochlorine pesticides in ginseng.

This study provides a review of methods used in the determination of organochlorine pesticides (OCPs) in ginseng and compares the effectiveness of three extraction methods (Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS), a modified QuEChERS and a Fast Pesticide Extraction (FaPEx)) in the analyses of 20 OCPs in ginseng root samples. For each method, sample mass, solvent volume and sorbent mass were varied to identify the optimum combination to effectively isolate analytes of interest from the complex sample matrix. Extracts were analyzed using the gas chromatography-µ-electron capture detector (GC-µ-ECD), and confirmatory analyses performed by gas chromatography-tandem-mass spectrometry (GC-MS/MS). Eighteen out of 20 OCPs spiked onto in-house prepared ginseng samples produced acceptable recoveries (51-156%) when extracted using QuEChERS and FaPEx. All 20 analytes, including dichlorodiphenyldichloroethane (p, p'- DDD) and dichlorodiphenyltrichloroethane (o, p'-DDT), produced acceptable recoveries (51-129%) with the use of a modified QuEChERS method. The applicability of the modified QuEChERS method was demonstrated through the analysis of ginseng samples grown in endosulfan-treated soil. The samples were analyzed by both GC-µ-ECD and GC-MS/MS with no significant difference identified in the results of each analytical method. This study highlights the applicability of the modified QuEChERS method, in combination with GC- µ-ECD, to determine organochlorine pesticides in ginseng. This may be especially useful for laboratories in developing countries and less advanced institutions without access to MS/MS instrumentation.

Development of new and selective Trypanosoma cruzi trans-sialidase inhibitors from sulfonamide chalcones and their derivatives.

A series of sulfonamide-containing hydroxylated chalcone (4-7) and quinolinone (8, 9) derivatives was synthesised and tested for inhibition of the trans-sialidase from Trypanosoma cruzi (TcTS). IC(50) values for these inhibitors ranged from 0.6 to 7.3 microM, with the dihydroxylated (catechol) derivatives being the tightest binders. Full kinetic analyses of inhibition were performed for these catechol derivatives, both for the transglycosylation reaction in the presence of lactose and for the hydrolysis reaction in its absence. Competitive inhibition was seen in each case with K(i) values for 5, 7 and 9 of 2.0, 2.2 and 0.2 microM, respectively, in the absence of lactose, and 4.6, 3.7 and 0.4 microM in its presence. None of the compounds tested showed any significant inhibition of the human sialidase Neu2, at concentrations up to 200 microM.

Characteristic of neuraminidase inhibitory xanthones from Cudrania tricuspidata.

Natural polyphenolic compounds generally transpire to show relatively low inhibition against glycosidase including neuraminidase. In addition the inhibition modes of such compounds are rarely competitive. In this manuscript, a series of xanthone derivatives from Cudrania tricuspidata are shown to display nanomolar inhibitor activity against neuraminidase (EC 3.2.1.18) as well as competitive inhibition modes. Compound 8 bearing vicinal dihydroxy group on the A-ring displays nanomolar activity (IC(50)=0.08+/-0.01 microM), a 200-fold increase in activity relative to that of the first reported xanthone-derived neuraminidase inhibitor, mangiferin (IC(50)=16.2+/-4.2 microM). The 6,7-vicinal dihydroxy group plays a crucial role for inhibitory activity because compound 4, which has one of these hydroxyl groups prenylated was inactive (33% at 200 microM), whereas other compounds (1-3 and 6-8) showed nanomolar activity (0.08-0.27 microM) and competitive inhibition modes. Interestingly all inhibitors manifested enzyme isomerization inhibition against neuraminidase. The most potent inhibitor, compound 8 showed similar interaction with a transition-state analogue of neuraminic acid in active site.

Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities.

Five flavonols (3, 5, and 9-11) were isolated from Rhodiola rosea, and compared with commercially available flavonoids (1, 2, 4, 6-8, and 12-14) to facilitate analysis of their structure-activity relationship (SAR). All compounds (1-14) showed neuraminidase inhibitory activities with IC(50) values ranging from 0.8 to 56.9 microM. The in vitro anti-influenza virus activities of flavonoids 1-6, 8-12, and 14 were evaluated using two influenza viral strains, H1N1 (A/PR/8/34) and H9N2 (A/Chicken/Korea/MS96/96), testing their ability to reduce virus-induced cytopathic effect (CPE) in MDCK cells. We found that the activity of these compounds ranged from 30.2 to 99.1 microM against H1N1- and 18.5 to 133.6 microM against H9N2-induced CPE. Of compounds 1-14, gossypetin (6) exhibited the most potent inhibitory activity, with IC(50) values of 0.8 and 2.6 microM on neuraminidases from Clostridium perfringens and recombinant influenza virus A (rvH1N1), respectively. In contrast, kaempferol (3) exhibited the highest activity against two influenza viruses, H1N1 and H9N2 with EC(50) values of 30.2 and 18.5 microM, respectively. Activity depended on the position and number of hydroxy groups on the flavonoids backbone. In kinetic studies, all isolated compounds behaved as noncompetitive inhibitors.