Inhibition of the metalloenzyme urease has important pharmacologic applications in the field of antiulcer and antigastric cancer agents. Urease is involved in many serious infections caused by Helicobacter pylori in the gastric tract as well as by Proteus and related species in the urinary tract. Although numerous studies have described several novel urease inhibitors (UIs) used for the treatment of gastric and urinary infections, all these compounds have exhibited severe side effects, toxicity, and instability. Therefore, to overcome such problems, it is necessary to search for new sources of UIs, such as natural products, that provide reduced side effects, low toxicity, greater stability, and bioavailability. As limited studies have been conducted on plant-derived UIs, this paper aims to highlight and summarize the most promising compounds isolated and identified from plants, such as terpenoids, phenolic compounds, alkaloids, and other substances with inhibitory activities against plant and bacterial ureases; these are in vitro and in vivo studies with an emphasis on structure-activity relationship studies and types of inhibition that show high and promising levels of anti-urease activity. This will aid medicinal chemists in the design and synthesis of novel and pharmacologically potent UIs useful for the development of antiulcer drugs.

• Klíčová slova
• Antiulcer drugs, Bioactive compounds, Gastric and urinary infections, Herbal plants, Urease inhibitors,
• MeSH
• Bacteria enzymologie   MeSH
• lidé MeSH
• protivředové látky analýza   izolace a purifikace   farmakologie   MeSH
• rostliny enzymologie   MeSH
• ureasa antagonisté a inhibitory   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• protivředové látky MeSH
• ureasa MeSH

Urease activity was detected in the dermatophyte Trichophyton mentagrophytes cells at early exponential phase of growth. Specific activity of urease decreased with culture age. At exogenous urea concentrations above 2 mM formation of urease was inhibited. The pH optimum lay at 7-7.5, the Km being 14 mM. No urease activity could be detected in cell-free culture fluid of T. mentagrophytes. No endo- or exocellular urease activity could be detected in a T. rubrum strain grown with or without urea.

• MeSH
• amoniak metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• močovina metabolismus   MeSH
• Trichophyton enzymologie   metabolismus   MeSH
• ureasa metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amoniak MeSH
• močovina MeSH
• ureasa MeSH

In experiments on six sheep fed on a low protein diet (6.2 g N/day), it was found that the urease activity of the rumen fluid did not change significantly in the first 6 hours after feeding and that it ranged from 45 to 75 nkat.ml-1. The major portion was bound to the bacterial fraction and formed about 70% of total rumen fluid activity. Urease activity determined in food particles with adherent bacteria removed from the rumen before and 3 and 6 hours after feeding ranged from 20 to 26 nkat.g-1 food (wet weight), and on rumen wall samples with adherent bacteria from 30 to 800 nkat per 2.5 cm2 tissue. Again, no significant changes correlated to the time after feeding were found. The results show that urease activity in the sheep rumen is localized on food particles and on rumen wall epithelium with adherent bacteria, as well as in the rumen fluid.

• MeSH
• amoniak metabolismus   MeSH
• bachor enzymologie   mikrobiologie   MeSH
• Bacteria enzymologie   MeSH
• časové faktory MeSH
• ovce MeSH
• ureasa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amoniak MeSH
• ureasa MeSH

In experiments on six sheep fed on a low nitrogen diet (3.7 g N/day), urease (EC 3.5.1.5) activity (nkat X mg-1 bacterial dry weight) 3 h after feeding was found to be highest in the bacteria adhering to the rumen wall (13.25 +/- 2.10), lower in the rumen fluid bacteria (8.96 +/- 1.35) and lowest in the bacteria adhering to feed particles in the rumen (5.69 +/- 2.13). The urease activity of bacteria adhering to the rumen wall and of the rumen fluid bacteria of six sheep fed on a high nitrogen diet (21 g N/day) was significantly lower than in sheep with a low N intake and in both cases was roughly the same (3.81 +/- 1.37 and 3.76 +/- 1.02 respectively); it was lowest in bacteria adhering to feed particles in the rumen (1.92 +/- 0.90). It is concluded from the results that the urease activity of rumen fluid bacteria and of bacteria adhering to the rumen wall and to feed particles in the rumen is different and that it falls significantly in the presence of a high nitrogen intake. From the relatively high ureolytic activity of bacteria adhering to the rumen wall in the presence of a low nitrogen intake it is assumed that this is one of the partial mechanisms of the hydrolysis of blood urea entering the rumen across the rumen wall and of its reutilization in the rumen-liver nitrogen cycle in ruminants.

• MeSH
• bachor enzymologie   MeSH
• Bacteria enzymologie   MeSH
• bakteriální adheze * MeSH
• dietní proteiny farmakologie   MeSH
• dusík farmakologie   MeSH
• krmivo pro zvířata MeSH
• ovce MeSH
• tělesné tekutiny enzymologie   MeSH
• ureasa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dietní proteiny MeSH
• dusík MeSH
• ureasa MeSH

It was originally shown [10] that urease retains its enzymatic activity when adsorbed at bare mercury and solid amalgam surfaces. However the opinion later prevailed that, when adsorbed at bare metal electrodes, proteins are irreversibly denatured. Here we confirm that urease is enzymatically active at a bare solid amalgam surface as found by Santhanam et al., and we show that this enzyme is equally active at a thiol-modified amalgam surface. We also show that it is the reduced form of urease, which is enzymatically active at Hg surfaces. Oxidation of the protein, resulting in formation of disulfide bonds, strongly decreases the enzyme activity. Using constant current chronopotentiometric stripping (CPS) we show that the exposure of surface-attached urease to negative potentials results in the protein unfolding. The extent of the unfolding depends upon the amount of time for which the protein is exposed to negative potentials, and at very short times this unfolding can be avoided. At thiol-modified Hg surfaces the protein is less vulnerable to the effects of the electric field. We conclude that the loss of enzymatic activity, resulting from a 10 min exposure of the protein to -0.58 V, is not due to reduction of the disulfide bonds as suggested by Santhanam et al. This loss is probably a result of protein reorientation, due to reduction of the Hg-S bonds (formed by accessible cysteines), followed by prolonged electric field effect on the surface-attached protein.

• Klíčová slova
• Constant-current chronopotentiometric stripping, Mercury containing electrodes, Protein denaturation at negatively charged surfaces, Protein structure at surfaces, Thiol-modified electrodes, Urease enzymatic activity,
• MeSH
• adsorpce MeSH
• cystein chemie   MeSH
• denaturace proteinů MeSH
• disulfidy chemie   MeSH
• dithiothreitol chemie   MeSH
• elektrochemické techniky MeSH
• elektrody MeSH
• katalýza MeSH
• oxidace-redukce MeSH
• povrchové vlastnosti MeSH
• rtuť chemie   MeSH
• sbalování proteinů MeSH
• sulfhydrylové sloučeniny chemie   MeSH
• teplota MeSH
• ureasa chemie   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cystein MeSH
• disulfidy MeSH
• dithiothreitol MeSH
• rtuť MeSH
• sulfhydrylové sloučeniny MeSH
• ureasa MeSH

The increasing resistance of pathogens to common antibiotics, as well as the need to control urease activity to improve the yield of soil nitrogen fertilization in agricultural applications, has stimulated the development of novel classes of molecules that target urease as an enzyme. In this context, the newly developed compounds on the basis of 1-heptanoyl-3-arylthiourea family were evaluated for Jack bean urease enzyme inhibition activity to validate their role as potent inhibitors of this enzyme. 1-Heptanoyl-3-arylthioureas were obtained in excellent yield and characterized through spectral and elemental analysis. All the compounds displayed remarkable potency against urease inhibition as compared to thiourea standard. It was found that novel compounds fulfill the criteria of drug-likeness by obeying Lipinski's rule of five. Particularly compound 4a and 4c can serve as lead molecules in 4D (drug designing discovery and development). Kinetic mechanism and molecular docking studies also carried out to delineate the mode of inhibition and binding affinity of the molecules.

• Klíčová slova
• Acyl thioureas, Antioxidant, Jack bean urease, Kinetic mechanism, Lipinski’s rules, Molecular modeling, Urease,
• MeSH
• Canavalia enzymologie   MeSH
• inhibitory enzymů chemie   farmakologie   MeSH
• kinetika MeSH
• molekulární struktura MeSH
• simulace molekulového dockingu * MeSH
• thiomočovina chemie   farmakologie   MeSH
• ureasa antagonisté a inhibitory   metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inhibitory enzymů MeSH
• thiomočovina MeSH
• ureasa MeSH

Herein, we present direct experimental evidence of pH oscillatory dynamics in the urea-urease enzymatic reaction conducted in a continuous reactor-membrane-reservoir system. Our results are consistent with earlier model predictions requiring differential transport of H+ and substrate. We report oscillations with periods in hundreds of seconds and the amplitude of ∼0.1 pH units.

• MeSH
• chemické modely MeSH
• gely chemie   MeSH
• kinetika MeSH
• koncentrace vodíkových iontů MeSH
• membrány umělé MeSH
• močovina chemie   MeSH
• ureasa chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• gely MeSH
• membrány umělé MeSH
• močovina MeSH
• ureasa MeSH

Urea, as an end product of protein metabolism and an abundant polar compound, significantly complicates the metabolomic analysis of urine by GC-MS. We developed a sample preparation method removing urea from urine samples prior the GC-MS analysis. The method based on urease immobilized on magnetic microparticles was compared with the others that are conventionally used (liquid-liquid extraction, free urease protocol), and samples without any treatment. To study the impact of sample preparation approaches on the quality of analytical data, we employed comprehensive metabolomic analysis (using both GC-MS and LC-MS/MS platforms) of standard material based on human urine. Multivariate statistical analysis has shown that immobilized urease treatment provides similar results to a free urease approach. However, significant alterations in the profiles of metabolites were observed in the samples without any treatment and after the extraction. Compared to other approaches that were tested, the immobilization of urease on microparticles reduces both the number of artifacts and the variability of the metabolites (average CV of extraction 19.7%, no treatment 11.4%, free urease 5.0%, and immobilized urease 2.5%). The method that was developed was applied in a GC-MS metabolomic experiment of glutaric aciduria type I, where both known diagnostically important biomarkers and unknowns, as the most discriminating compounds, were found.

• Klíčová slova
• GC–MS, Immobilized urease, Metabolomics, Urine sample preparation,
• MeSH
• analýza hlavních komponent MeSH
• chromatografie kapalinová metody   MeSH
• enzymy imobilizované moč   MeSH
• glutaryl-CoA-dehydrogenasa nedostatek   metabolismus   MeSH
• lidé MeSH
• magnetické jevy * MeSH
• metabolické nemoci mozku metabolismus   MeSH
• metabolom MeSH
• metabolomika metody   MeSH
• metody pro přípravu analytických vzorků * MeSH
• močovina metabolismus   MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí metody   MeSH
• reprodukovatelnost výsledků MeSH
• studie proveditelnosti MeSH
• tandemová hmotnostní spektrometrie MeSH
• ureasa moč   MeSH
• vrozené poruchy metabolismu aminokyselin metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• enzymy imobilizované MeSH
• glutaryl-CoA-dehydrogenasa MeSH
• močovina MeSH
• ureasa MeSH

Studies on enzyme inhibition remain a crucial area in drug discovery since these studies have led to the discoveries of new lead compounds useful in the treatment of several diseases. In this study, protocatechuic acid (PCA), an active compound from Hibiscus sabdariffa L. has been evaluated for its inhibitory properties against jack bean urease (JBU) as well as its possible toxic effect on human gastric epithelial cells (GES-1). Anti-urease activity was evaluated by an Electrospray Ionization-Mass Spectrometry (ESI-MS) based method, while cytotoxicity was assayed by the MTT method. PCA exerted notable anti-JBU activity compared with that of acetohydroxamic acid (AHA), with IC50 values of 1.7 and 3.2 µM, respectively. PCA did not show any significant cytotoxic effect on (GES-1) cells at concentrations ranging from 1.12 to 3.12 µM. Molecular docking study revealed high spontaneous binding ability of PCA to the active site of urease. Additionally, the anti-urease activity was found to be related to the presence of hydroxyl moieties of PCA. This study presents PCA as a natural urease inhibitor, which could be used safely in the treatment of diseases caused by urease-producing bacteria.

• Klíčová slova
• ESI-Mass spectrometry, Hibiscus sabdariffa L., cytotoxicity, molecular docking, protocatechuic acid, urease inhibitors,
• MeSH
• buněčné linie MeSH
• Hibiscus chemie   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
• hydroxybenzoáty chemie   MeSH
• kyseliny hydroxamové chemie   MeSH
• lidé MeSH
• simulace molekulového dockingu metody   MeSH
• ureasa antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetohydroxamic acid MeSH Prohlížeč
• hydroxybenzoáty MeSH
• kyseliny hydroxamové MeSH
• protocatechuic acid MeSH Prohlížeč
• ureasa MeSH

• MeSH
• Ascomycota enzymologie   MeSH
• Basidiomycota enzymologie   MeSH
• Candida enzymologie   MeSH
• Cryptococcus enzymologie   MeSH
• deoxyribonukleasy metabolismus   MeSH
• kvasinky klasifikace   enzymologie   MeSH
• Pichia enzymologie   MeSH
• ribonukleasy metabolismus   MeSH
• Saccharomyces enzymologie   MeSH
• ureasa metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• deoxyribonukleasy MeSH
• ribonukleasy MeSH
• ureasa MeSH