urease enzyme Dotaz Zobrazit nápovědu
Vnásledujícím souhrnu je uveden přehled dostupné literatury na aktuální téma týkající se enzymu ureasy. Ureasa je enzym katalyzující hydrolýzu močoviny. Vpřehledu je diskutován výskyt ureasy, její funkce avýznam arovněž role ureasy aureolytických bakterií vpatogenezi různých onemocnění. Jsou prezentovány známé anorganické ipřírodní inhibitory ureasy. Práce se zabývá důležitostí hledání nových inhibitorů ureasy apotenciálem přírodních látek vtéto oblasti.
In this review, an overview of the available literature on urease is presented. Urease is an enzyme which catalyzes the hydrolysis of urea. The occurrence of ureases and their functions are discussed thoroughly. The relationship of urease to ureolytic bacteria is examined, and the currently available urease inhibitors, both inorganic and natural, are presented. Finally, the importance of urease and current and future applications of new inhibitors and explored.
- MeSH
- Helicobacter pylori imunologie patogenita MeSH
- inhibitory enzymů klasifikace MeSH
- Klebsiella imunologie patogenita MeSH
- lidé MeSH
- moč * mikrobiologie MeSH
- močové ústrojí * mikrobiologie MeSH
- močovina * MeSH
- nádory farmakoterapie MeSH
- Proteus imunologie patogenita MeSH
- rostlinné extrakty MeSH
- ureasa * antagonisté a inhibitory fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy 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.
- 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
AIMS: The aim of the present research was to synthesize glycoluril derivative 2,4-Bis(4- cyanobenzyl)glycoluril through a convergent scheme. BACKGROUND: For this purpose, Sandmeyer reaction procedure was employed for the synthesis of said compound. The structure of the pure compound was confirmed by using different spectroscopic techniques, such as 1HNMR, 13C-NMR and (HR-MS) Mass spectrometry. OBJECTIVE: Convergent synthesis of 2,4-BIS (4-CYANOBENZYL)GLYCOLURIL USING SANDMEYER REACTION and urease inhibition study. METHODS: The structure of the pure compound was confirmed by using different spectroscopic techniques such as 1H-NMR, 13C-NMR and (HR-MS) Mass spectrometry. The electronic properties of the newly synthesized compound and thiourea were determined by using density functional theory. RESULTS: Furthermore, the compound was evaluated against urease enzyme and was found to be potent inhibitors with an IC50 value of 11.5 ± 1.50 μM when compared with standard inhibitor thiourea (IC50 = 21.0 ± 1.90 μM). The compound may serve as a lead compound to synthesize new cyano-based bambusuril in the future with enhanced biological properties. CONCLUSION: We have synthesized a new glycoluril derivative 2,4-Bis(4-cyanobenzyl)glycoluril by the sandmeyer reaction. It has been obtained in the form of light yellowish powder in good yield (96%). Glycoluril based macrocycles have been used in various fields; starting from the 2,4-Bis(4-nitrobenzyl)glycoluril (already reported compound), which has undergone reduction (CH3OH,Pt/C) , diazotization (NaNO2/HCl), cyanation (CuCl/KCN), respectively in order to synthesize the desired new glycoluril derivative. The obtained product will be used as a building block for the synthesis of the cyano based bambusuril marcocycle in the future. The yield of the obtained product has been monitored by using different amounts of cyanating reagent, but the best results are shown by the use of 4 mmol of CuCl/KCN. KCN with CuCl assisted the conversion of diazo group into the cyano group with enhanced yield when used in excess amount. It acts as a catalyst. The solubility characteristic of 2,4-Bis(4-cyanobenzyl)glycoluril has also been determined in different organic solvents. 1H NMR technique proved to be very helpful for the structure determination of our desired product. Benzylic protons give signals at 7.5 ppm and 7.8 ppm, respectively. The downfield peaks confirm the presence of CN group near the benzylic protons. Methine protons show a signal at 5.2 ppm, which ensures the basic skeleton of glycoluril. Ureidyl protons also confirm the synthesis of the heterocyclic 2,4-Bis(4-cyanobenzyl)glycoluril compound. The negative and positive electrostatic potential sites, molecular descriptors, and charge density distribution of frontier molecular orbitals are revealing that 4a with promising sites for electrophilic and nucleophilic attacks would result to enhance the urease inhibition, which is in good agreement with the experimental data.
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.
- 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
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.
- 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
In the current study, pyroglutamic acid (pGlu), a natural amino acid derivative, has efficiently inhibited the catalytic activities of three important enzymes, namely: Human recombinant phosphodiesterase-5A1 (PDE5A1), human angiotensin-converting enzyme (ACE), and urease. These enzymes were reported to be associated with several important clinical conditions in humans. Radioactivity-based assay, spectrophotometric-based assay, and an Electrospray Ionization-Mass Spectrometry-based method were employed to ascertain the inhibitory actions of pGlu against PDE5A1, ACE, and urease, respectively. The results unveiled that pGlu potently suppressed the activity of PDE5A1 (half-maximal inhibitory concentration; IC50 = 5.23 µM) compared with that of standard drug sildenafil citrate (IC50 = 7.14 µM). Moreover, pGlu at a concentration of 20 µg/mL was found to efficiently inhibit human ACE with 98.2% inhibition compared with that of standard captopril (99.6%; 20 µg/mL). The urease-catalyzed reaction was also remarkably inactivated by pGlu and standard acetohydroxamic acid with IC50 values of 1.8 and 3.9 µM, respectively. Remarkably, the outcome of in vitro cytotoxicity assay did not reveal any significant cytotoxic properties of pGlu against human cervical carcinoma cells and normal human fetal lung fibroblast cells. In addition to in vitro assays, molecular docking analyses were performed to corroborate the outcomes of in vitro results with predicted structure-activity relationships. In conclusion, pGlu could be presented as a natural and multifunctional agent with promising applications in the treatment of some ailments connected with the above-mentioned anti-enzymatic properties.
- MeSH
- angiotensin konvertující enzym chemie genetika metabolismus MeSH
- buněčné linie MeSH
- cyklické nukleotidfosfodiesterasy, typ 5 chemie genetika metabolismus MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- inhibiční koncentrace 50 MeSH
- kaptopril chemie metabolismus MeSH
- kyselina pyrrolidonkarboxylová chemie metabolismus toxicita MeSH
- kyseliny hydroxamové antagonisté a inhibitory metabolismus MeSH
- lidé MeSH
- rekombinantní proteiny biosyntéza chemie izolace a purifikace MeSH
- sildenafil citrát chemie metabolismus MeSH
- simulace molekulového dockingu MeSH
- spektrofotometrie MeSH
- terciární struktura proteinů MeSH
- ureasa antagonisté a inhibitory metabolismus MeSH
- vazebná místa MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS)-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC50 values of 0.92 and 1.43 µg∙mL(-1), respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC50 value of 82.4 µg∙mL(-1). This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.
- MeSH
- acyklovir farmakologie MeSH
- antivirové látky chemie izolace a purifikace farmakologie MeSH
- Cercopithecus aethiops MeSH
- Hibiscus chemie MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- inhibiční koncentrace 50 MeSH
- inhibitory enzymů chemie izolace a purifikace farmakologie MeSH
- kinetika MeSH
- lidský herpesvirus 2 účinky léků MeSH
- polyfenoly chemie izolace a purifikace farmakologie MeSH
- preklinické hodnocení léčiv MeSH
- rostlinné extrakty chemie izolace a purifikace farmakologie MeSH
- ureasa antagonisté a inhibitory chemie MeSH
- Vero buňky MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Furan chalcone scaffolds belong to the most privileged and promising oxygen-containing heterocyclic class of compounds, which have a wide spectrum of therapeutic applications in the field of pharmaceutics, pharmacology, and medicinal chemistry. This research described the synthesis of a series of twelve novel and seven reported furan chalcone (conventional synthetic approach) analogues 4a-s through the application of microwave-assisted synthetic methodology and evaluated for therapeutic inhibition potential against bacterial urease enzyme. In the first step, a series of nineteen substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were achieved in moderate to good yields (40-70%). These substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were condensed with acetophenone via Claisen-Schmidt condensation to furnish 19 substituted furan chalcone scaffolds 4a-s in excellent yields (85-92%) in microwave-assisted synthetic approach, while in conventional methodology, these furan chalcone 4a-s were furnished in good yield (65-90%). Furan chalcone structural motifs 4a-s were characterized through elemental analysis and spectroscopic techniques. These nineteen (19)-afforded furan chalcones 4a-s were screened for urease inhibitory chemotherapeutic efficacy and most of the furan chalcones displayed promising urease inhibition activity. The most active urease inhibitors were 1-phenyl-3-[5-(2',5'-dichlorophenyl)-2-furyl]-2-propen-1-one 4h with an IC50 value of 16.13 ± 2.45 μM, and 1-phenyl- 3-[5-(2'-chlorophenyl)-2-furyl] -2-propen-1-one 4s with an IC50 value of 18.75 ± 0.85 μM in comparison with reference drug thiourea (IC50 = 21.25 ± 0.15 μM). These furan chalcone derivatives 4h and 4s are more efficient urease inhibitors than reference drug thiourea. Structure-activity relationship (SAR) revealed that the 2,5-dichloro 4h and 2-chloro 4s moiety containing furan chalcone derivatives may be considered as potential lead reagents for urease inhibition. The in silico molecular docking study results are in agreement with the experimental biological findings. The results of this study may be helpful in the future drug discovery and designing of novel efficient urease inhibitory agents from this biologically active class of furan chalcones.
- Publikační typ
- časopisecké články MeSH
