Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A new urease inhibitor from Viola betonicifolia.

ABSTRACT: Urease has attracted much attention, as it is directly involved in the formation of infection stones and contributes to the pathogenesis of urolithiasis, pyelonephritis, ammonia and hepatic encephalopathy, hepatic coma and urinary catheter encrustation. Moreover, urease is the major cause of pathologies induced by H. pylori, such as gastritis and peptic ulcer. In the present work, the new natural compound, 3-methoxydalbergione, was isolated from Viola betonicifolia. A mechanistic study of this compound as a natural urease inhibitor was performed by using enzyme kinetics and docking studies. 3-Methoxydalbergione could be considered as a lead molecule for drugs useful in the urease associated diseases.

SUBMITTER: Muhammad N

PROVIDER: S-EPMC6270924 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A new urease inhibitor from Viola betonicifolia.

Muhammad Naveed N Saeed Muhammad M Khan Ajmal A Adhikari Achyut A Wadood Abdul A Khan Khalid Mohammed KM De Feo Vincenzo V

Molecules (Basel, Switzerland) 20141017 10

Urease has attracted much attention, as it is directly involved in the formation of infection stones and contributes to the pathogenesis of urolithiasis, pyelonephritis, ammonia and hepatic encephalopathy, hepatic coma and urinary catheter encrustation. Moreover, urease is the major cause of pathologies induced by H. pylori, such as gastritis and peptic ulcer. In the present work, the new natural compound, 3-methoxydalbergione, was isolated from Viola betonicifolia. A mechanistic study of this c ...[more]

PMID: 25329870

Similar Datasets

Transcriptomic changes in maize roots triggered by urease inhibitor NBPT

Project description:In the soil the stability of urea is affected by the presence of urease, a ubiquitous enzyme released in the rhizosphere by microbial population and by decomposition of organic matter. To reduce the impact on farmer economies and environmental pollution, a common agronomical practice consists of applying urease inhibitors which delays the hydrolysis of urea and, in turn, ammonia is slowly release in the soil. General aim of the present work was the description of changes in maize root transcriptome occurring in response to treatment with the urease inhibitor NBPT.

2017-02-09 | GSE76828 | GEO

Viola kauaensis var. hosakae (Violaceae), a new variety of endemic Hawaiian violet.

Project description:The Hawaiian endemic Viola kauaensis A. Gray has a broad distribution in bogs of Kaua`i and a limited distribution on mesic ridges in the Ko`olau Mountains of O`ahu. Based on differences in scale, the O`ahu populations of Viola kauaensis had previously been described as a distinct taxon. The taxonomic status of the O`ahu populations was reevaluated through a morphometric analysis of all varieties of Viola kauaensis and the morphologically similar Viola vanroyenii. Morphological features of historic and freshly collected specimens of all varieties of Viola kauaensis were analyzed with a principal components analysis. Populations from O`ahu represent a distinct cluster that slightly overlaps with Viola kauaensis var. kauaensis. Lamina width, apex angle, and base angles contribute to the separation of the O`ahu populations from other varieties of Viola kauaensis. Due to differences in scale, the O`ahu populations are described as Viola kauaensis var. hosakae, a new critically endangered taxon.

| S-EPMC4152890 | biostudies-other

Metallochaperone UreG serves as a new target for design of urease inhibitor: A novel strategy for development of antimicrobials.

Project description:Urease as a potential target of antimicrobial drugs has received considerable attention given its versatile roles in microbial infection. Development of effective urease inhibitors, however, is a significant challenge due to the deeply buried active site and highly specific substrate of a bacterial urease. Conventionally, urease inhibitors are designed by either targeting the active site or mimicking substrate of urease, which is not efficient. Up to now, only one effective inhibitor-acetohydroxamic acid (AHA)-is clinically available, but it has adverse side effects. Herein, we demonstrate that a clinically used drug, colloidal bismuth subcitrate, utilizes an unusual way to inhibit urease activity, i.e., disruption of urease maturation process via functional perturbation of a metallochaperone, UreG. Similar phenomena were also observed in various pathogenic bacteria, suggesting that UreG may serve as a general target for design of new types of urease inhibitors. Using Helicobacter pylori UreG as a showcase, by virtual screening combined with experimental validation, we show that two compounds targeting UreG also efficiently inhibited urease activity with inhibitory concentration (IC)50 values of micromolar level, resulting in attenuated virulence of the pathogen. We further demonstrate the efficacy of the compounds in a mammalian cell infection model. This study opens up a new opportunity for the design of more effective urease inhibitors and clearly indicates that metallochaperones involved in the maturation of important microbial metalloenzymes serve as new targets for devising a new type of antimicrobial drugs.

| S-EPMC5779714 | biostudies-literature

A Novel Urease Inhibitor of Ruminal Microbiota Screened through Molecular Docking.

Project description:Inhibition of the urease activity of ruminal microbiota is not only beneficial for increasing dietary and endogenic urea-N utilization efficiency in ruminants but also might be applicable for the preservation of nitrogen fertilizer in soil and treatment of gastrointestinal and urinary tract infections caused by ureolytic bacteria. To discover urease inhibitors to efficiently target ruminal microbiota, the identified ruminal microbial metagenomic urease gene was used to construct a homology model to virtually screen urease inhibitors from the ChemDiv database by molecular docking. The GMQE and QMEAN values of the homology model were 0.85 and -0.37, respectively, indicating a good model quality. The inhibition effect of the screened urease inhibitor for ruminal urea degradation was assessed by ruminal microbial fermentation in vitro. The toxic effect of the candidate inhibitor was performed using gut Caco-2 cells in vitro. The results showed that compound 3-[1-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-1H-pyrrol-2-yl] propanoic acid (ChemDiv_ID: 6238-0047, IC50 = 65.86 μM) was found to be the most effective urease inhibitor among the candidate compounds. Compound 6238-0047 significantly lowered the amount of urea degradation and ammonia production in ruminal microbial fermentation. The 24 h degradation rate of compound 6238-0047 in ruminal microbial fermentation was 3.32%-16.00%. In addition, compound 6238-0047 (10-100 μM) had no significant adverse effect on the cell viability of Caco-2 cells. Molecular docking showed that compound 6238-0047 could interact with Asp359 in the active site and Cys318 in the flap region by the hydrogen bond and Pi-Alkyl interaction, respectively. Compound 6238-0047 could be used as a novel inhibitor for decreasing the urease activity of ruminal microbiota.

| S-EPMC7503308 | biostudies-literature

A new species of Viola (Violaceae) from Guangdong Province, China.

Project description:Viola huizhouensis (Violaceae), a new species from Xiangtoushan National Nature Reserve of Guangdong Province in China, is described and illustrated. The new species is most similar to V. guangzhouensis, but it can be easily distinguished by its much stouter rhizome, lack of aerial stem, dense pubescence of the basal pedicel and the whole plant. Our phylogenetic analysis, based on ITS sequences, confirms that the new species belongs to V. sect. Diffusae.

| S-EPMC8065024 | biostudies-literature

Synthesis of diindolylmethane (DIM) bearing thiadiazole derivatives as a potent urease inhibitor.

Project description:The current study describes synthesis of diindolylmethane (DIM) derivatives based-thiadiazole as a new class of urease inhibitors. Diindolylmethane is natural product alkaloid reported to use in medicinal chemistry extensively. Diindolylmethane-based-thiadiazole analogs (1-18) were synthesized and characterized by various spectroscopic techniques 1HNMR, 13C-NMR, EI-MS and evaluated for urease (jack bean urease) inhibitory potential. All compounds showed excellent to moderate inhibitory potential having IC50 value within the range of 0.50 ± 0.01 to 33.20 ± 1.20 µM compared with the standard thiourea (21.60 ± 0.70 µM). Compound 8 (IC50 = 0.50 ± 0.01 µM) was the most potent inhibitor amongst all derivatives. Structure-activity relationships have been established for all compounds. The key binding interactions of most active compounds with enzyme were confirmed through molecular docking studies.

| S-EPMC7224224 | biostudies-literature

Chelerythrine Chloride: A Potential Rumen Microbial Urease Inhibitor Screened by Targeting UreG.

Project description:Inhibition of ruminal microbial urease is of particular interest due to its crucial role in regulating urea-N utilization efficiency and nitrogen pollution in the livestock industry. Acetohydroxamic acid (AHA) is currently the only commercially available urease inhibitor, but it has adverse side effects. The urease accessory protein UreG, which facilitates the functional incorporation of the urease nickel metallocentre, has been proposed in developing urease inhibitor through disrupting urease maturation. The objective of this study was to screen natural compounds as potential urease inhibitors by targeting UreG in a predominant ruminal microbial urease. In silico screening and in vitro tests for potential inhibitors were performed using molecular docking and an assay for the GTPase activity of UreG. Chelerythrine chloride was selected as a potential urease inhibitor of UreG with an inhibition concentration IC50 value of 18.13 μM. It exhibited mixed inhibition, with the Ki value being 26.28 μM. We further explored its inhibition mechanism using isothermal titration calorimetry (ITC) and circular dichroism (CD) spectroscopy, and we found that chelerythrine chloride inhibited the binding of nickel to UreG and induced changes in the secondary structure, especially the α-helix and β-sheet of UreG. Chelerythrine chloride formed a pi-anion interaction with the Asp41 residue of UreG, which is an important residue in initiating the conformational changes of UreG. In conclusion, chelerythrine chloride exhibited a potential inhibitory effect on urease, which provided new evidence for strategies to develop novel urease inhibitors targeting UreG to reduce nitrogen excretion from ruminants.

| S-EPMC8347364 | biostudies-literature

Recent advances in design of new urease inhibitors: A review.

Project description:Urease is a nickel-dependent metalloenzyme found in plants, some bacteria, and fungi. Bacterial enzyme is of special importance since it has been demonstrated as a potent virulence factor for some species. Especially it is central to Helicobacter pylori metabolism and virulence being necessary for its colonization of the gastric mucosa, and is a potent immunogen that elicits a vigorous immune response. Therefore, it is not surprising that efforts to design, synthesize and evaluate of new inhibitors of urease are and active field of medicinal chemistry. In this paper recent advances on this field are reviewed.

| S-EPMC6077125 | biostudies-literature

Agronomic efficiency of NBPT as a urease inhibitor: A review.

Project description:Urea is the most widely used nitrogen (N) fertilizer, with a projected increase in annual demand of 1.5% in the coming years. After its application to soil, urea undergoes hydrolysis via the urease enzyme, causing increases in the soil pH in the surrounding area of the granules and resulting in NH3 losses that average 16% of N applied worldwide and can reach 40% or more in hot and humid conditions. The use of urease inhibitors is an effective way to reduce NH3 losses. Several compounds act as urease inhibitors, but only N-(n-butyl) thiophosphoric triamide (NBPT) has been used worldwide, being the most successful in a market that has grown 16% per year in the past 10?years. Only in the past three years other compounds are being commercially launched. In comparison to urea, NBPT-treated urea reduces NH3 loss by around 53%. Yield gain by NBPT usage is of the order of 6.0% and varies from -0.8 to 10.2% depending on crop species. Nitrification inhibitors usually increase NH3 volatilization and mixing them with urease inhibitors partially offsets the benefits of the latter in reducing NH3 loss. The efficacy of NBPT to reduce NH3 loss is well documented, but there is a need for further improvement to increase the period of inhibition and the shelf life of NBPT-treated urea.

| S-EPMC6077139 | biostudies-other

Synthesis and Identification of New N,N-Disubstituted Thiourea, and Thiazolidinone Scaffolds Based on Quinolone Moiety as Urease Inhibitor.

Project description:Synthesis of thiazolidinone based on quinolone moiety was established starting from 4-hydroxyquinol-2-ones. The strategy started with the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding N,N-disubstituted thioureas. Finally, on subjecting the N,N-disubstituted thioureas with dialkyl acetylenedicarboxylates, cyclization occurred, and thiazolidinone derivatives were obtained in good yields. The two series based on quinolone moiety, one containing N,N-disubstituted thioureas and the other containing thiazolidinone functionalities, were screened for their in vitro urease inhibition properties using thiourea and acetohydroxamic acid as standard inhibitors. The inhibition values of the synthesized thioureas and thiazolidinones exhibited moderate to good inhibitory effects. The structure-activity relationship revealed that N-methyl quinolonyl moiety exhibited a superior effect, since it was proved to be the most potent inhibitor in the present series achieving (IC50 = 1.83 ± 0.79 µM). The previous compound exhibited relatively much greater activity, being approximately 12-fold more potent than thiourea and acetohydroxamic acid as references. Molecular docking analysis showed a good protein-ligand interaction profile against the urease target (PDBID: 4UBP), emphasizing the electronic and geometric effect of N,N-disubstituted thiourea.

| S-EPMC9608620 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data