The Experts below are selected from a list of 2412 Experts worldwide ranked by ideXlab platform
Hailiang Zhu - One of the best experts on this subject based on the ideXlab platform.
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synthesis structure activity relationship analysis and kinetics study of reductive derivatives of flavonoids as helicobacter pylori Urease Inhibitors
European Journal of Medicinal Chemistry, 2013Co-Authors: Zhuping Xiao, Zhiyun Peng, Jingjun Dong, Hui Ouyang, Yuting Feng, Wanqiang Lin, Jinxiang Wang, Yinping Xiang, Hailiang ZhuAbstract:In a continuing study for discovering Urease Inhibitors based on flavonoids, nineteen reductive derivatives of flavonoids were synthesized and evaluated against Helicobacter pylori Urease. Analysis of structure-activity relationship disclosed that 4-deoxy analogues are more potent than other reductive products. Out of them, 4',7,8-trihydroxyl-2-isoflavene (13) was found to be the most active with IC50 of 0.85 μM, being over 20-fold more potent than the commercial available Urease Inhibitor, acetohydroxamic acid (AHA). Kinetics study revealed that 13 is a competitive Inhibitor of H. pylori Urease with a Ki value of 0.641 μM, which is well matched with the results of molecular docking. Biological evaluation and mechanism study of 13 suggest that it is a good candidate for discovering novel anti-gastritis and anti-gastric ulcer agent.
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molecular docking kinetics study and structure activity relationship analysis of quercetin and its analogous as helicobacter pylori Urease Inhibitors
Journal of Agricultural and Food Chemistry, 2012Co-Authors: Zhuping Xiao, Zhiyun Peng, Xudong Wang, Shen Huang, Pan Yang, Lihu Zhou, Yin Zhou, Hailiang ZhuAbstract:It was disclosed in our group for the first time that the flavonoids in Lonicera japonica Thunb. are related to its therapy for gastric ulcer. Based on this finding, 20 flavonoids were selected for Helicobacter pylori Urease Inhibitory activity evaluation, and quercetin showed excellent potency with IC(50) of 11.2 ± 0.9 μM. Structure-activity relationship analysis revealed that removal of the 5-, 3-, or 3'-OH in quercetin led to a sharp decrease in activity. Thus, 3- and 5-OH as well as 3',4'-dihydroxyl groups are believed to be the key structural characteristics for active compounds, which was supported by the molecular docking study. Meanwhile, the results obtained from molecular docking and enzymatic kinetics research strongly suggested that quercetin is a noncompetitive Urease Inhibitor, indicating that quercetin may be able to tolerate extensive structural modification irrespective of the shape of the active site cavity and could be used as a lead candidate for the development of novel Urease Inhibitors.
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the synthesis structure and activity evaluation of pyrogallol and catechol derivatives as helicobacter pylori Urease Inhibitors
European Journal of Medicinal Chemistry, 2010Co-Authors: Zhuping Xiao, Xiaochun Peng, Aihua Zhang, Hailiang ZhuAbstract:Abstract Some pyrogallol and catechol derivatives were synthesized, and their Urease Inhibitory activity was evaluated by using acetohydroxamic acid (AHA), a well known Helicobacter pylori Urease Inhibitor, as positive control. The assay results indicate that many compounds have showed potential Inhibitory activity against H. pylori Urease. 4-(4-Hydroxyphenethyl)phen-1,2-diol ( 2a ) was found to be the most potent Urease Inhibitor with IC 50 s of 1.5 ± 0.2 μM for extracted fraction and 4.2 ± 0.3 μM for intact cell, at least 10 times and 20 times lower than those of AHA (IC 50 of 17.2 ± 0.9 μM, 100.6 ± 13 μM), respectively. This finding indicate that 2a would be a potential Urease Inhibitor deserves further research. Molecular dockings of 2a into H. pylori Urease active site were performed for understanding the good activity observed.
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synthesis molecular docking and biological evaluation of metronidazole derivatives as potent helicobacter pylori Urease Inhibitors
Bioorganic & Medicinal Chemistry, 2009Co-Authors: Wenjun Mao, Lei Shi, Hailiang ZhuAbstract:Abstract Fourteen metronidazole derivatives (compounds 3a – f and 4b – h ) have been synthesized by coupling of metronidazole and salicylic acid derivatives. All of them are reported for the first time. Their chemical structures are characterized by 1 H NMR, MS, and elemental analysis. The Inhibitory activities against Helicobacter pylori Urease have been investigated in vitro and many compounds have showed promising potential Inhibitory activities of H. pylori Urease. The effect of compounds 4b (IC 50 = 26 μM) and 4g (IC 50 = 12 μM) was comparable with that of acetohydroxamic acid, a well known H. pylori Urease Inhibitor used as a positive control. The experimental values of IC 50 showed that Inhibitor was potent Urease Inhibitor. A docking analysis using the autodock 4.0 program could explain the Inhibitory activities of compound 4g against H. pylori Urease.
Antonio Vallejo - One of the best experts on this subject based on the ideXlab platform.
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meta analysis of the effect of Urease and nitrification Inhibitors on crop productivity and nitrogen use efficiency
Agriculture Ecosystems & Environment, 2014Co-Authors: Diego Abalos, Alberto Sanzcobena, Simo Jeffery, Guillermo Guardia, Antonio VallejoAbstract:Abstract Nitrification and Urease Inhibitors are proposed as means to reduce nitrogen losses, thereby increasing crop nitrogen use efficiency (NUE). However, their effect on crop yield is variable. A meta-analysis was conducted to evaluate their effectiveness at increasing NUE and crop productivity. Commonly used nitrification Inhibitors (dicyandiamide (DCD) and 3,4-dimethylepyrazole phosphate (DMPP)) and the Urease Inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) were selected for analysis as they are generally considered the best available options. Our results show that their use can be recommended in order to increase both crop yields and NUE (grand mean increase of 7.5% and 12.9%, respectively). However, their effectiveness was dependent on the environmental and management factors of the studies evaluated. Larger responses were found in coarse-textured soils, irrigated systems and/or crops receiving high nitrogen fertilizer rates. In alkaline soils (pH ≥ 8), the Urease Inhibitor NBPT produced the largest effect size. Given that their use represents an additional cost for farmers, understanding the best management practices to maximize their effectiveness is paramount to allow effective comparison with other practices that increase crop productivity and NUE.
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effectiveness of Urease inhibition on the abatement of ammonia nitrous oxide and nitric oxide emissions in a non irrigated mediterranean barley field
Chemosphere, 2012Co-Authors: Diego Abalos, Alberto Sanzcobena, T H Misselbrook, Antonio VallejoAbstract:Urea is considered the cheapest and most commonly used form of inorganic N fertilizer worldwide. However, its use is associated with emissions of ammonia (NH(3)), nitrous oxide (N(2)O) and nitric oxide (NO), which have both economic and environmental impact. Urease activity Inhibitors have been proposed as a means to reduce NH(3) emissions, although limited information exists about their effect on N(2)O and NO emissions. In this context, a field experiment was carried out with a barley crop (Hordeum vulgare L.) under Mediterranean conditions to test the effectiveness of the Urease Inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) on reducing these gaseous N losses from surface applied urea. Crop yield, soil mineral N concentrations, dissolved organic carbon (DOC), denitrification potential, NH(3), N(2)O and NO fluxes were measured during the growing season. The inclusion of the Inhibitor reduced NH(3) emissions in the 30 d following urea application by 58% and net N(2)O and NO emissions in the 95 d following urea application by 86% and 88%, respectively. NBPT addition also increased grain yield by 5% and N uptake by 6%, although neither increase was statistically significant. Under the experimental conditions presented here, these results demonstrate the potential of the Urease Inhibitor NBPT in abating NH(3), N(2)O and NO emissions from arable soils fertilized with urea, slowing urea hydrolysis and releasing lower concentrations of NH(4)(+) to the upper soil layer.
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effect of water addition and the Urease Inhibitor nbpt on the abatement of ammonia emission from surface applied urea
Atmospheric Environment, 2011Co-Authors: Alberto Sanzcobena, T H Misselbrook, Vicci Camp, Antonio VallejoAbstract:Abstract Urea is considered the cheapest and most commonly used form of inorganic N fertiliser worldwide. However, it has been estimated that 5–30% of the urea N is lost as volatilised NH3. Implementation of NH3 mitigation strategies is crucial in order to reduce both the economic and environmental impact associated with NH3 losses from urea application. Urease activity Inhibitors and water addition to the soil have been proposed by UNECE (i.e. Gothenburg Protocol) as means to reduce NH3 emission from fertiliser applications. In this study, two field experiments were carried out in order to test the effectiveness of water addition as NH3 mitigation technique from surface applied urea in comparison with the use of the Urease Inhibitor NBPT. A system of wind tunnels was used to measure NH3 fluxes. Contrasting irrigation strategies (or rainfall patterns), in terms of both rate and timing, were used in order to evaluate the amount of water necessary to achieve a significant NH3 mitigation. The addition of 7 and 14 mm of water to the soil, immediately after urea spreading, reduced NH3 emission by 77 and 89%, respectively, similar to that achieved using NBPT (77–88% reduction). In contrast, a simulated 3 mm rainfall, immediately after fertilising, significantly enhanced NH3 volatilisation (with an 8% increase in emission compared to urea application without water addition). These results demonstrate the potential of correct water management in abating NH3 volatilisation from urea applications to soil, giving a similar effect to that of the Urease Inhibitor NBPT under the experimental conditions presented here.
Zhuping Xiao - One of the best experts on this subject based on the ideXlab platform.
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synthesis structure activity relationship analysis and kinetics study of reductive derivatives of flavonoids as helicobacter pylori Urease Inhibitors
European Journal of Medicinal Chemistry, 2013Co-Authors: Zhuping Xiao, Zhiyun Peng, Jingjun Dong, Hui Ouyang, Yuting Feng, Wanqiang Lin, Jinxiang Wang, Yinping Xiang, Hailiang ZhuAbstract:In a continuing study for discovering Urease Inhibitors based on flavonoids, nineteen reductive derivatives of flavonoids were synthesized and evaluated against Helicobacter pylori Urease. Analysis of structure-activity relationship disclosed that 4-deoxy analogues are more potent than other reductive products. Out of them, 4',7,8-trihydroxyl-2-isoflavene (13) was found to be the most active with IC50 of 0.85 μM, being over 20-fold more potent than the commercial available Urease Inhibitor, acetohydroxamic acid (AHA). Kinetics study revealed that 13 is a competitive Inhibitor of H. pylori Urease with a Ki value of 0.641 μM, which is well matched with the results of molecular docking. Biological evaluation and mechanism study of 13 suggest that it is a good candidate for discovering novel anti-gastritis and anti-gastric ulcer agent.
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molecular docking kinetics study and structure activity relationship analysis of quercetin and its analogous as helicobacter pylori Urease Inhibitors
Journal of Agricultural and Food Chemistry, 2012Co-Authors: Zhuping Xiao, Zhiyun Peng, Xudong Wang, Shen Huang, Pan Yang, Lihu Zhou, Yin Zhou, Hailiang ZhuAbstract:It was disclosed in our group for the first time that the flavonoids in Lonicera japonica Thunb. are related to its therapy for gastric ulcer. Based on this finding, 20 flavonoids were selected for Helicobacter pylori Urease Inhibitory activity evaluation, and quercetin showed excellent potency with IC(50) of 11.2 ± 0.9 μM. Structure-activity relationship analysis revealed that removal of the 5-, 3-, or 3'-OH in quercetin led to a sharp decrease in activity. Thus, 3- and 5-OH as well as 3',4'-dihydroxyl groups are believed to be the key structural characteristics for active compounds, which was supported by the molecular docking study. Meanwhile, the results obtained from molecular docking and enzymatic kinetics research strongly suggested that quercetin is a noncompetitive Urease Inhibitor, indicating that quercetin may be able to tolerate extensive structural modification irrespective of the shape of the active site cavity and could be used as a lead candidate for the development of novel Urease Inhibitors.
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the synthesis structure and activity evaluation of pyrogallol and catechol derivatives as helicobacter pylori Urease Inhibitors
European Journal of Medicinal Chemistry, 2010Co-Authors: Zhuping Xiao, Xiaochun Peng, Aihua Zhang, Hailiang ZhuAbstract:Abstract Some pyrogallol and catechol derivatives were synthesized, and their Urease Inhibitory activity was evaluated by using acetohydroxamic acid (AHA), a well known Helicobacter pylori Urease Inhibitor, as positive control. The assay results indicate that many compounds have showed potential Inhibitory activity against H. pylori Urease. 4-(4-Hydroxyphenethyl)phen-1,2-diol ( 2a ) was found to be the most potent Urease Inhibitor with IC 50 s of 1.5 ± 0.2 μM for extracted fraction and 4.2 ± 0.3 μM for intact cell, at least 10 times and 20 times lower than those of AHA (IC 50 of 17.2 ± 0.9 μM, 100.6 ± 13 μM), respectively. This finding indicate that 2a would be a potential Urease Inhibitor deserves further research. Molecular dockings of 2a into H. pylori Urease active site were performed for understanding the good activity observed.
Alberto Sanzcobena - One of the best experts on this subject based on the ideXlab platform.
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meta analysis of the effect of Urease and nitrification Inhibitors on crop productivity and nitrogen use efficiency
Agriculture Ecosystems & Environment, 2014Co-Authors: Diego Abalos, Alberto Sanzcobena, Simo Jeffery, Guillermo Guardia, Antonio VallejoAbstract:Abstract Nitrification and Urease Inhibitors are proposed as means to reduce nitrogen losses, thereby increasing crop nitrogen use efficiency (NUE). However, their effect on crop yield is variable. A meta-analysis was conducted to evaluate their effectiveness at increasing NUE and crop productivity. Commonly used nitrification Inhibitors (dicyandiamide (DCD) and 3,4-dimethylepyrazole phosphate (DMPP)) and the Urease Inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) were selected for analysis as they are generally considered the best available options. Our results show that their use can be recommended in order to increase both crop yields and NUE (grand mean increase of 7.5% and 12.9%, respectively). However, their effectiveness was dependent on the environmental and management factors of the studies evaluated. Larger responses were found in coarse-textured soils, irrigated systems and/or crops receiving high nitrogen fertilizer rates. In alkaline soils (pH ≥ 8), the Urease Inhibitor NBPT produced the largest effect size. Given that their use represents an additional cost for farmers, understanding the best management practices to maximize their effectiveness is paramount to allow effective comparison with other practices that increase crop productivity and NUE.
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effectiveness of Urease inhibition on the abatement of ammonia nitrous oxide and nitric oxide emissions in a non irrigated mediterranean barley field
Chemosphere, 2012Co-Authors: Diego Abalos, Alberto Sanzcobena, T H Misselbrook, Antonio VallejoAbstract:Urea is considered the cheapest and most commonly used form of inorganic N fertilizer worldwide. However, its use is associated with emissions of ammonia (NH(3)), nitrous oxide (N(2)O) and nitric oxide (NO), which have both economic and environmental impact. Urease activity Inhibitors have been proposed as a means to reduce NH(3) emissions, although limited information exists about their effect on N(2)O and NO emissions. In this context, a field experiment was carried out with a barley crop (Hordeum vulgare L.) under Mediterranean conditions to test the effectiveness of the Urease Inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) on reducing these gaseous N losses from surface applied urea. Crop yield, soil mineral N concentrations, dissolved organic carbon (DOC), denitrification potential, NH(3), N(2)O and NO fluxes were measured during the growing season. The inclusion of the Inhibitor reduced NH(3) emissions in the 30 d following urea application by 58% and net N(2)O and NO emissions in the 95 d following urea application by 86% and 88%, respectively. NBPT addition also increased grain yield by 5% and N uptake by 6%, although neither increase was statistically significant. Under the experimental conditions presented here, these results demonstrate the potential of the Urease Inhibitor NBPT in abating NH(3), N(2)O and NO emissions from arable soils fertilized with urea, slowing urea hydrolysis and releasing lower concentrations of NH(4)(+) to the upper soil layer.
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effect of water addition and the Urease Inhibitor nbpt on the abatement of ammonia emission from surface applied urea
Atmospheric Environment, 2011Co-Authors: Alberto Sanzcobena, T H Misselbrook, Vicci Camp, Antonio VallejoAbstract:Abstract Urea is considered the cheapest and most commonly used form of inorganic N fertiliser worldwide. However, it has been estimated that 5–30% of the urea N is lost as volatilised NH3. Implementation of NH3 mitigation strategies is crucial in order to reduce both the economic and environmental impact associated with NH3 losses from urea application. Urease activity Inhibitors and water addition to the soil have been proposed by UNECE (i.e. Gothenburg Protocol) as means to reduce NH3 emission from fertiliser applications. In this study, two field experiments were carried out in order to test the effectiveness of water addition as NH3 mitigation technique from surface applied urea in comparison with the use of the Urease Inhibitor NBPT. A system of wind tunnels was used to measure NH3 fluxes. Contrasting irrigation strategies (or rainfall patterns), in terms of both rate and timing, were used in order to evaluate the amount of water necessary to achieve a significant NH3 mitigation. The addition of 7 and 14 mm of water to the soil, immediately after urea spreading, reduced NH3 emission by 77 and 89%, respectively, similar to that achieved using NBPT (77–88% reduction). In contrast, a simulated 3 mm rainfall, immediately after fertilising, significantly enhanced NH3 volatilisation (with an 8% increase in emission compared to urea application without water addition). These results demonstrate the potential of correct water management in abating NH3 volatilisation from urea applications to soil, giving a similar effect to that of the Urease Inhibitor NBPT under the experimental conditions presented here.
Ping Huang - One of the best experts on this subject based on the ideXlab platform.
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inhibition of helicobacter pylori and its associated Urease by palmatine investigation on the potential mechanism
PLOS ONE, 2017Co-Authors: Jiangtao Zhou, Ping Huang, Lihua Tan, Yuhong Liu, Yaoxing Dou, Jianhui XieAbstract:In this paper, we evaluated the anti-Helicobacter pylori activity and the possible Inhibitory effect on its associated Urease by Palmatine (Pal) from Coptis chinensis, and explored the potential underlying mechanism. Results indicated that Pal exerted Inhibitory effect on four tested H. pylori strains (ATCC 43504, NCTC 26695, SS1 and ICDC 111001) by the agar dilution test with minimum Inhibitory concentration (MIC) values ranging from 100 to 200 μg/mL under neutral environment (pH 7.4), and from 75 to 100 μg/mL under acidic conditions (pH 5.3), respectively. Pal was observed to significantly inhibit both H. pylori Urease (HPU) and jack bean Urease (JBU) in a dose-dependent manner, with IC50 values of 0.53 ± 0.01 mM and 0.03 ± 0.00 mM, respectively, as compared with acetohydroxamic acid, a well-known Urease Inhibitor (0.07 ± 0.01 mM for HPU and 0.02 ± 0.00 mM for JBU, respectively). Kinetic analyses showed that the type of Urease inhibition by Pal was noncompetitive for both HPU and JBU. Higher effectiveness of thiol protectors against Urease inhibition than the competitive Ni2+ binding Inhibitors was observed, indicating the essential role of the active-site sulfhydryl group in the Urease inhibition by Pal. DTT reactivation assay indicated that the inhibition on the two Ureases was reversible, further supporting that sulfhydryl group should be obligatory for Urease inhibition by Pal. Furthermore, molecular docking study indicated that Pal interacted with the important sulfhydryl groups and inhibited the active enzymatic conformation through N-H ∙ π interaction, but did not interact with the active site Ni2+. Taken together, Pal was an effective Inhibitor of H. pylori and its Urease targeting the sulfhydryl groups, representing a promising candidate as novel Urease Inhibitor. This investigation also gave additional scientific support to the use of C. chinensis to treat H. pylori-related gastrointestinal diseases in traditional Chinese medicine. Pal might be a potentially beneficial therapy for gastritis and peptic ulcers induced by H. pylori infection and other Urease-related diseases.
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biological evaluation and molecular docking of baicalin and scutellarin as helicobacter pylori Urease Inhibitors
Journal of Ethnopharmacology, 2015Co-Authors: Rongbo Zheng, Jianhui Xie, Xiaoqi Huang, Yonghong Wang, Yifeng Zheng, Yeer Liang, Huifang Zeng, Ping HuangAbstract:Abstract Ethnopharmacological relevance Baicalin and scutellarin are the principal bioactive components of Scutellaria baicalensis Georgi which has extensively been incorporated into heat-clearing and detoxification formulas for the treatment of Helicobacter pylori-related gastrointestinal disorders in traditional Chinese medicine. However, the mechanism of action remained to be defined. Aim of the study To explore the Inhibitory effect, kinetics and mechanism of Helicobacter pylori Urease (the vital pathogenetic factor for Helicobacter pylori infection) inhibition by baicalin and scutellarin, for their therapeutic potential. Materials and methods The ammonia formations, indicator of Urease activity, were examined using modified spectrophotometric Berthelot (phenol–hypochlorite) method. The Inhibitory effect of baicalin and scutellarin was characterized with IC50 values, compared to acetohydroxamic acid (AHA), a well known Helicobacter pylori Urease Inhibitor. Lineweaver–Burk and Dixon plots for the Helicobacter pylori Urease inhibition of baicalin and scutellarin was constructed from the kinetic data. SH-blocking reagents and competitive active site Ni2+ binding Inhibitors were employed for mechanism study. Molecular docking technique was used to provide some information on binding conformations as well as confirm the inhibition mode. Moreover, cytotoxicity experiment using Gastric Epithelial Cells (GES-1) was evaluated. Results Baicalin and scutellarin effectively suppressed Helicobacter pylori Urease in dose-dependent and time-independent manner with IC50 of 0.82±0.07 mM and 0.47±0.04 mM, respectively, compared to AHA (IC50=0.14±0.05 mM). Structure-activity relationship disclosed 4′-hydroxyl gave flavones an advantage to binding with Helicobacter pylori Urease. Kinetic analysis revealed that the types of inhibition were non-competitive and reversible with inhibition constant Ki of 0.14±0.01 mM and 0.18±0.02 mM for baicalin and scutellarin, respectively. The mechanism of Urease inhibition was considered to be blockage of the SH groups of Helicobacter pylori Urease, since thiol reagents ( l , d -dithiothreitol, l -cysteine and glutathione) abolished the Inhibitory action and competitive active site Ni2+ binding Inhibitors (boric acid and sodium fluoride) carried invalid effect. Molecular docking study further supported the structure-activity analysis and indicated that baicalin and scutellarin interacted with the key residues Cys321 located on the mobile flap through S H·π interaction, but did not interact with active site Ni2+. Moreover, Baicalin (at 0.59–1.05 mM concentrations) and scutellarin (at 0.23–0.71 mM concentrations) did not exhibit significant cytotoxicity to GES-1. Conclusions Baicalin and scutellarin were non-competitive Inhibitors targeting sulfhydryl groups especially Cys321 around the active site of Helicobacter pylori Urease, representing potential to be good candidate for future research as Urease Inhibitor for treatment of Helicobacter pylori infection. Furthermore, our work gave additional scientific support to the use of Scutellaria baicalensis in traditional Chinese medicine (TCM) to treat gastrointestinal disorders.
