Urease Inhibitors Research Articles

The effect of three urease inhibitors on H. pylori viability, urease activity and urease gene expression

BackgroundTreatment of Helicobacter pylori (H. pylori) infections is challenged by antibiotic resistance. The urease enzyme contributes to H. pylori colonization in the gastric acidic environment by producing a neutral microenvironment. We hypothesized that urease inhibition could affect H. pylori viability. This work aimed to assess the effects of acetohydroxamic acid (AHA), ebselen and baicalin on urease activity, bacterial viability and urease genes expression in H. pylori isolates.MethodsForty-nine H. pylori clinical isolates were collected. Urease activity was assessed using the phenol red method. The urease inhibition assay assessed inhibitors' effects on urease activity. Flow cytometry assessed the effect of inhibitors on bacterial viability. Real time PCR was used to compare urease genes expression levels following urease inhibition.ResultsUrease activity levels differed between isolates. Acetohydroxamic acid inhibited urease activity at a concentration of 2.5 mM. Although baicalin inhibited urease activity at lower concentrations, major effects were seen at 8 mM. Ebselen's major inhibition was demonstrated at 0.06 mM. Baicalin (8 mM) significantly reduced ATP production compared to untreated isolates. Baicalin, ebselen and acetohydroxamic acid significantly reduced H. pylori viability. Increased urease genes expression was detected after exposure to all urease inhibitors.DiscussionIn conclusion, higher concentrations of baicalin were needed to inhibit urease activity, compared to acetohydroxamic acid and ebselen. Baicalin, ebselen and acetohydroxamic acid reduced H. pylori viability. Therefore, these inhibitors should be further investigated as alternative treatments for H. pylori infection.

Corrigendum: Field efficacy of urease inhibitors for mitigation of ammonia emissions in agricultural field settings: a systematic review

Corrigendum: Field efficacy of urease inhibitors for mitigation of ammonia emissions in agricultural field settings: a systematic review

Optimizing Nitrogen Management in Maize (Zea mays L.) Using Urease and Nitrification Inhibitorss

ABSTRACT Nitrogen (N) is essential for plant growth, and in conventional agriculture, it is usually supplied through fertilization. However, N can be lost through various pathways, reducing its availability to plants and decreasing fertilizer efficiency. This study examined the effects of split urea application and fertilizers containing the nitrification inhibitor 3.4-dimethylpyrazole phosphate (DMPP) and the urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT). The fertilizers with inhibitors were applied at both full (100%) and reduced (75%) levels of the standard rate. Conducted over two years, the field trial aimed to assess the capacity of these treatments to mitigate N loss and meet the N requirements of maize effectively. The results of the study revealed that NBPT maintained the required N levels in the soil by meeting the N requirement of maize. On the other hand, DMPP caused N losses due to increasing ammonium levels in the soil during early plant growth stages. NBPT provided the best results in terms of plant yield and N content, whereas DMPP showed lower performance in these parameters. Reduced NBPT doses increased N use efficiency but were less effective in terms of yield compared to full doses. According to the result of the economic analysis, split urea treatment gave better results compared to all treatments. In conclusion, NBPT increased both yield and N use efficiency by regulating N release.

A Urease‐Based pH Photoswitch: A General Route to Light‐to‐pH Transduction

AbstractNew approaches for the integration of chemical and physical stimuli to control the dynamics of artificial enzymatic reaction networks (ERNs) are needed. Here, we present a general approach to convert a light stimulus into a time‐programmed pH response. We developed and characterized a panel of photoswitchable inhibitors of urease. Urease activity, now regulated by light via the photoinhibitors, leads to an increase in pH upon hydrolysis of urea into ammonia. Careful choice of characteristics of light, and concentrations of enzyme, substrate, and photoinhibitor, allowed us to control the timing of the pH transition. Furthermore, as all enzymes have an activity–pH profile, the urease photoinhibitor system can be used to regulate the activities of other enzymes in small reaction networks.

Successful NH3 abatement policies and regulations in German agriculture

Anthropogenic ammonia (NH3) emissions, of which about 95 % are from agriculture, have led to environmental pollution, resulting in tremendous damage to human health and ecosystems. Thus, the NEC Directive 2016/2284/EU sets national reduction targets for NH3 emissions in individual EU countries. To implement the NEC Directive for NH3 emission targets, Germany amended the Fertilizer Application Ordinance in 2017 and 2020 (DüV_amended) and set the air pollution control regulation, Technical Instructions on Air Quality Control (TA_Luft). This study aimed to evaluate the impact of the DüV_amended on NH3 mitigation from applying livestock manure, digestates, synthetic nitrogen (N) fertilizers, and TA_Luft on housing and storage. This study showed that Germany reached the first national NH3 reduction target in 2020, as set by the NEC directive. The German DüV_amended, a significant policy change, has profoundly impacted NH3 emission mitigation from agriculture after 2017 by implementing measures aimed directly at NH3 reduction, reducing N surpluses, and improving N use efficiency. The reduction in NH3 emissions from synthetic N fertilizers between 2016 and 2022 contributed about 51 % to the decrease from the agricultural sector over the same period. Among the synthetic fertilizers, NH3 reduction from urea between 2016 and 2022 accounted for around 83 % of the total reduction from synthetic N, indicating that the NH3 emissions from urea fertilizer by reducing urea application and mandating urea to be incorporated immediately or to be stabilized with urease inhibitors played a crucial role in the sharp decrease in NH3 emissions over the last years in Germany. Achieving a high yield by lowering the synthetic N rate in this study strongly suggests that optimal reduction in N rate does not necessarily result in yield losses but rather in a pivotal relationship between the agronomic and environmental performance and indicates that the DüV_amended was an effective measure that can reduce the NH3 emissions.Over 80 % of Germany's annual agricultural NH3 emissions in 2021 and 2022 originated from livestock and digestates from energy crops. Mandatory close to the soil band application of slurry and digestates on cultivated cropland since 2020 reduced NH3 emissions. In addition, banning of broadcast application of slurry to grassland and manure incorporation within one hour on uncultivated soils will become mandatory in 2025 to comply with NEC 2030´s target of 29 % NH3 reduction relative to 2005. The recent German air pollution control regulation (TA_Luft) enforces abatement measures such as air purifiers in large poultry and pig housings and covered storage of slurry and digestate storages of large farms. The results of the German NH3 abatement strategy for synthetic N fertilizers may help reduce NH3 emissions worldwide, especially for countries consuming high amounts of urea fertilizers.

Investigation of Algerian Crataegus monogyna Jacq Phenolic Compounds (Using LC-ESI-MS/MS Analysis, Antioxidant Activity, and Enzyme Inhibition) and Their Potential Implications for Food and Nutraceutical Applications

Investigations into the phenolic constituents of the butanolic fraction of Crataegus monogyna were optimized using LC-ESI-MS/MS analysis, identifying and quantifying at least 23 fingerprint phytochemical compounds. The major phenolic compounds were epicatechin (99.916 ± 2.208 mg/g), isoquercetrin (53.31 ± 1.172 mg/g), chlorogenic acid (47.457 ± 1.010 mg/g), quinic acid (37.819 ± 1.406 mg/g), rutin (29.98 ± 0.740 mg/g), hesperidin (5.296 ± 0.177 mg/g, detected for the first time in the C. monogyna species), astragalin (1.774 ± 0.020 mg/g), and nicotiflorin (1.482 ± 0.016 mg/g). The antioxidant properties of the lyophilized butanolic fraction were evaluated using DPPH, GOR, ABTS, CUPRAC, and reducing power assays, all of which demonstrated that there was strong activity. Additionally, the neuroprotective effect was evaluated in vitro, showing a potent inhibitory effect on acetylcholinesterase (AChE) with an IC50 of 43.65 ± 2.10 µg/mL. The antidiabetic effect was investigated through α-amylase inhibition (IC50 = 91.19 ± 0.10 µg/mL), showing high inhibitory activity. In addition, the butanolic extract exhibited significant urease inhibition with an IC50 of 26.36 ± 0.05 µg/mL. These results suggest that Algerian C. monogyna has potential as a therapeutic agent for managing diabetes complications and as a natural source of AChE inhibitors, making it a promising subject for the treatment of urease-related conditions. Its high concentrations of natural antioxidants, such as epicatechin, isoquercetrin, chlorogenic acid, quinic acid, rutin, hesperidin, and astragalin, make it suitable for integration into medicine, pharmaceuticals, cosmetics, and the food sector.

Multifunctional effects of nitrification and urease inhibitors: decreasing soil herbicide residues and reducing nitrous oxide emissions simultaneously

Glyphosate pollution and greenhouse gas emissions are major problem in achieving sustainable soil management. It is necessary to develop effective strategies to simultaneously reduce herbicide residues and nitrous oxide (N2O) emissions in soil. This study aimed to: (1) quantitative analyze the effects of nitrogen (N) cycle inhibitors (nitrification inhibitors 3,4 dimethylpyrazole phosphate (DMPP) and dicyandiamide (DCD) and urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT)) on glyphosate degradation and reduction of N2O under different soil moistures; (2) identify the functional microbes and genes associated with glyphosate degradation and N2O emissions; and (3) decipher the main mechanisms of N cycle inhibitors affecting glyphosate degradation at different soil water contents. Compared to the control, the application of DMPP, DCD and NBPT reduced glyphosate residues in soil by 33.0%, 60.3% and 35.7%, respectively, under 90% water holding capacity (WHC). The application of DCD stimulated Acidobacteria and the phnX gene to degrade soil glyphosate. Further, soil glyphosate residues were significantly and negatively related to soil N2O emissions at both 60% and 90% WHC. Compared to the control, NBPT application decreased cumulative N2O emissions by 91.4% at 90% WHC by decreasing soil nitrate N (NO3--N) and inhibiting amoC and narG genes at 90%. The application of N cycle inhibitors could be a potential strategy to simultaneously reduce glyphosate residues and soil N2O emissions. Our study could provide technical support to reduce the risks of herbicide exposure and reduce greenhouse gas emissions.

Hydroxamic Acids Derivatives: Greener Synthesis, Antiureolytic Properties And Potential Medicinal Chemistry Applications - A Concise Review.

Hydroxamic acids (HAs) are chemical compounds characterized by the general structure RCONR'OH, where R and R' can denote hydrogen, aryl, or alkyl groups. Recognized for their exceptional chelating capabilities, HAs can form mono or bidentate complexes through oxygen and nitrogen atoms, rendering them remarkably versatile. These distinctive structural attributes have paved the way for a broad spectrum of medicinal applications for HAs, among which their pivotal role as inhibitors of essential Ni(II) and Zn(II)-containing metalloenzymes. In 1962, a significant breakthrough occurred when Kobashi and colleagues identified hydroxamic acids (HAs) as potent urease inhibitors. Subsequent research has increasingly underscored their capability in combatting infections induced by ureolytic microorganisms, including Helicobacter pylori and Proteus mirabilis. However, comprehensive reviews exploring their potential applications in treating infections caused by ureolytic microorganisms remain scarce in the scientific literature. Thus, this minireview aims to bridge this gap by offering a systematic exploration of the subject. Furthermore, it seeks to explore the significant advancements in obtaining hydroxamic acid derivatives through environmentally sustainable methodologies.

Selecting an optimal sorghum cultivar can improve nitrogen availability and wheat yield in crop rotation.

Sorghum (Sorghum bicolor L. Moench) is a cereal crop known for its biological nitrification inhibition (BNI) capacity, a plant-mediated activity limiting nitrification pathway. The use of BNI-producing plants represents an environmentally friendly and cost-effective approach to reduce nitrogen (N) losses, such as nitrate (NO3 -) leaching and nitrous oxide (N2O) gas emissions. The present study aimed to test the effectiveness of different S. bicolor cultivars in rotation to retain ammonium (NH4 +) in soils and promote N availability for the subsequent wheat crop. A two-year field rotation was established with four sorghum cultivars followed by winter wheat (Triticum aestivum L.). Urea alone or combined with the urease inhibitor N-(n-butyl) thiophosphoric triamide was applied to promote a NH4 +-based fertilization regimes. AddingN-(n-butyl) thiophosphoric triamide maintained higher soil NH4 + content and reduced ammonia-oxidizing bacteria population during sorghum cultivation. However, the benefits of the inhibitor on sorghum growth were cultivar-dependent. Notably, the further reduction in ammonia-oxidizing bacteria abundance for sorghum Voyenn and the increased soil NH4 + content for Vilomene suggested a BNI potential for these cultivars. Importantly, the Vilomene precedent enhanced wheat yield for both fertilization regimes. Overall, the present study confirms that sorghum is a suitable catch crop and emphasizes the importance of selecting the proper sorghum cultivar to maximize the yield of the target wheat crop, at the same time as minimizing N losses. Furthermore, developing combined strategies with selected sorghum cultivars and the application of urease inhibitors enables to enhance sorghum productivity as forage, achieving added value to the rotation. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

The Effect of the Use of a Novel Urease Inhibitor Coated Urea on the Greenhouse Gas Emissions and Ammonia Volatilization Losses from a Maize Field

Nitrogen fertilizers are essential for enhancing agricultural productivity but are also major contributors to greenhouse gas (GHG) emissions and ammonia volatilization, which affect environmental sustainability. This study evaluated the effect of cashew nut shell liquid (CNSL)-coated urea on GHG emissions and ammonia losses from maize fields in the Indo-Gangetic Plains, known for excessive nitrogen fertilizer usage. A randomized block design was employed with four treatments: control (no nitrogen), prilled urea, neem-coated urea (NCU), and CNSL-coated urea (CCU). Gas samples were collected using the closed chamber method, and emissions of CO₂ and N₂O were analyzed via gas chromatography. Ammonia volatilization was measured using the forced air draft method. Results showed that the CCU treatment significantly reduced ammonia volatilization compared to prilled urea (15.84% reduction), with reductions of 9% to those observed with NCU. Moreover, CCU-treated plots exhibited reduced cumulative GHG and lower global warming potential (GWP) without compromising maize yields. Cumulative GHG emissions varied among the treatments in the order urea> CCU> NCU> Control. CCU treated plots exhibited a net GWP decrease of 8.59% compared to urea and an increase of 4.13% compared to NCU. These findings suggest that CNSL-coated urea can serve as an eco-friendly alternative to conventional urea, potentially mitigating environmental impacts associated with nitrogen fertilization. Further studies are recommended to assess the long-term efficacy of CNSL in various soil types and climatic conditions.

Urease inhibition stimulates fungal degradation of chitin in frass‐amended soil

AbstractBackgroundThe by‐product of insect larval production, frass, can be applied to soil as an organic fertiliser. Its three main organic N fractions are assumed to be ureic, protein and chitin. The significance of the latter is unknown, and it is not known if lignaceous sources have been overlooked.AimsThis study sought to gauge the activities of the (respectively, lignolytic and chitinolytic) enzymes peroxidase and N‐acetyl‐ß‐D‐glucosaminidase following frass application to soil. Their activities were monitored under conditions of urease inhibition, with a particular focus on the fungal domain.MethodsMealworm or buffalo worm frass was applied, with or without inhibitors, to a sand/soil substrate at 3% (w/w). After 16 weeks, concentrations of the fungal biomarker ergosterol and enzyme activities were determined.ResultsSoil amendment with frass had no significant effect on peroxidase activity. Fungal biomass was stimulated in particular by application of mealworm frass, which was further improved by urease inhibition. Chitinase activity was positively correlated with fungal biomass, and was increased under urease inhibition when applied with mealworm frass.ConclusionsThere were no appreciable quantities of lignaceous compounds in the frass used in this study. Importantly, the use of urease inhibitors co‐applied with frass has demonstrated that when its ureic N breakdown is prevented, chitin becomes a significant organic N source to soil fungi. The superior fungal response to mealworm frass indicates a larger chitin content than in buffalo worm frass.

Synthesis of newly designed hydrazones, in vitro and in silico studies, and structure-activity relationship

Herein, new N'-(substituted benzylidene)-3,5-dihydroxybenzohydrazide (1–13) series were synthesized, and their antioxidant, anticholinesterase, anti-tyrosinase, anti-urease, and antidiabetic activities were investigated together with in silico studies. The synthesized derivates were characterized using molecular spectroscopy, and the structure-activity relationships (SAR) were discussed for all tested biological assays. According to activity results, compound 3 exhibited excellent antioxidant activity in all tests, while compound 1 demonstrated the best acetylcholinesterase (AChE) inhibitory and butyrylcholinesterase (BChE) inhibitory activities. On the other hand, compound 11 showed excellent tyrosinase inhibitory (IC50:3.02±0.10 mM) and urease inhibitory (IC50:9.21±0.27 µM) activity. Moreover, among the synthesized compounds, compound 6 was detected as the best antidiabetic compound by inhibiting α-amylase (IC50:30.68±0.94 µM) and α-glycosidase (IC50:41.35±0.03 µM) enzymes, which were related with the antidiabetic activity. Molecular docking analysis confirmed AChE, BChE, tyrosinase, urease, α-amylase, and α-glucosidase inhibitory activities. In line with the findings obtained from in vitro bioactivity results and molecular docking analysis, hydrazone compounds are a suitable class of organic compounds for developing acetylcholinesterase, butyrylcholinesterase, urease, α-amylase, and α-glucosidase inhibitors.

Synthesis, Urease Inhibition, Molecular Docking, and Optical Analysis of a Symmetrical Schiff Base and Its Selected Metal Complexes.

Designing and developing small organic molecules for use as urease inhibitors is challenging due to the need for ecosystem sustainability and the requirement to prevent health risks related to the human stomach and urinary tract. Moreover, imaging analysis is widely utilized for tracking infections in intracellular and in vivo systems, which requires drug molecules with emissive potential, specifically in the low-energy region. This study comprises the synthesis of a Schiff base ligand and its selected transition metals to evaluate their UV/fluorescence properties, inhibitory activity against urease, and molecular docking. Screening of the symmetrical cage-like ligand and its metal complexes with various eco-friendly transition metals revealed significant urease inhibition potential. The IC50 value of the ligand for urease inhibition was 21.80 ± 1.88 µM, comparable to that of thiourea. Notably, upon coordination with transition metals, the ligand-nickel and ligand-copper complexes exhibited even greater potency than the reference compound, with IC50 values of 11.8 ± 1.14 and 9.31 ± 1.31 µM, respectively. The ligand-cobalt complex exhibited an enzyme inhibitory potential comparable with thiourea, while the zinc and iron complexes demonstrated the least activity, which might be due to weaker interactions with the investigated protein. Meanwhile, all the metal complexes demonstrated a pronounced optical response, which could be utilized for fluorescence-guided targeted drug delivery applications in the future. Molecular docking analysis and IC50 values from in vitro urease inhibition screening showed a trend of increasing activity from compounds 7d to 7c to 7b. Enzyme kinetics studies using the Lineweaver-Burk plot indicated mixed-type inhibition against 7c and non-competitive inhibition against 7d.

Fabrication of two novel two-dimensional copper-based coordination polymers regulated by the “V”-shaped second auxiliary ligands as high-efficiency urease inhibitors

Two novel copper-based coordination polymers (Cu-CPs) had been presented based on mixed ligands. The synthetic Cu-CP-1 and Cu-CP-2 were derived from a combination of two distinct forms of “V”-shaped bis-pyridine-bis-amide ligands and 1,2,4-benzenetricarboxylic acid (1,2,4-H3BTC). Distinct grid windows were seen in the simplified two-dimensional (2D) layers of the Cu-CPs due to the variable length of ligand regulation. These Cu-CPs had the potential to act as urease inhibitors (UIs), and the mechanisms responsible for their inhibition were extensively studied. The results indicated that both Cu-CPs exhibited significant urease inhibitory activities with urease inhibition rates of 88.02 % and 88.87 % at 100 µM and semi-inhibitory levels of IC50 of 0.92 ± 0.05 µM and 0.87 ± 0.03 µM, respectively. Furthermore, the inhibitory activities of the Cu-CPs were higher than those of the standard thiourea. An investigation of the enzyme kinetics of the Cu-CPs using Lineweaver–Burk (L–B) plots at various inhibitor doses demonstrated their non-competitive inhibitory nature, enhancing our comprehension of the possible mechanism by which these Cu-CPs exert urease inhibition. Furthermore, molecular docking was used to verify the interactions between Cu-CPs and the urease active site. The findings of the urease inhibition studies were good, and the impact of Cu-CP complexes on urease inhibition was examined using density functional theory (DFT) simulations.

Nutrient recovery from urine: Urea adsorption onto biochar integrated with Na-chabazite as urease inhibitor

This study presents an innovative technical integration for concomitant nutrient recovery from source-separated urine. While cation exchange is known for efficient K+ recovery, it faces competition due to the high molarity of NH4+ in hydrolyzed urine. This study proposes inhibiting urease activity to facilitate the recovery of K⁺ and urea from fresh urine. Na-chabazite was first proposed as a urease inhibitor in this study, reducing urease activity by 50 %. Wood biochar, with its high porosity (308.0 m²/g) and polar functional groups, shows a urea adsorption capacity of 25.4 mg/g, which can be further improved by steam activation. The isotherm analysis suggests that urea adsorption onto biochar follows a multi-layer adsorption process. Finally, an integrated process is suggested: "Na-chabazite and Biochar adsorption → urea hydrolysis → struvite precipitation + ammonia stripping-acid scrubbing", ensuring efficient recovery of urea, NH4+, PO43-, and K+ from source-separated urine.

Synthesis, spectral characterization and biological activities of o,o'-dihydroxyazo compounds containing gallic acid: Molecular docking and dynamics simulation and MM-PBSA studies

In the investigation, diazonium derivatives of 2-aminophenol, 2-amino-4-methylphenol, 2-amino-4-chlorophenol, and 2-amino-5-nitrophenol reacted with gallic acid to produce four distinct o,o'-dihydroxyazo compounds. Description of the o,o'-dihydroxyazo compounds that were produced identified the substituent spectrum data using UV–Vis, FT-IR, NMR spectroscopy and MS spectrometry methods. The UV–Vis behaviors of compounds in ethanol and DMSO were noted at various pH values. The antioxidant, antimicrobial, and urease inhibitory activities of the compounds were determined spectrophotometrically and compared to standard compounds. The DPPH˙ scavenging and metal chelating activities of compound 4b were 2.17 ± 0.04 and 11.62 ± 0.64 μg/mL, respectively. Compounds exhibited an effective antibacterial activity against B. cereus. The urease inhibition capacity of compound 4c (IC50: 4.79 ± 0.01 μg/mL) was more effective than thiourea (IC50: 20.04 ± 0.16 μg/mL). Moreover, molecular docking calculations were used to assess the urease inhibition potentials, inhibition kinetics, and interactions of the synthesized compounds with antimicrobial enzymes and urease. The compounds had substantial impacts on density functional theory (DFT), molecular electrostatic potential (MEP), inhibition kinetics, enzyme inhibition, and PASS prediction tests. For this reason, molecular dynamics simulation and MM-PBSA energy calculation were performed to assess the compounds' stability during urease binding.As a result, the effective pharmacological properties of the newly synthesized o,o'-dihydroxyazo compounds were revealed by different in vitro bioactivity tests and in silico calculations.

Molecular Docking and Molecular Dynamics Simulations of the Urease Inhibitory Activity of 2,3‐Dihydroxybenzohydrazide Derivatives

AbstractThis investigation focuses on a suite of 2,3‐dihydroxybenzoyl hydrazine derivative ligands, examining their viability as urease activity inhibitors and delving into their operative mechanisms. Utilizing molecular docking approaches, the binding patterns and interactive loci of 2,3‐dihydroxybenzoyl hydrazine derivatives with urease were elucidated. The origin of the binding forces between the ligands and urease, along with pertinent descriptors, were scrutinized through an amalgamation of density functional theory calculations and molecular dynamics simulations. The findings indicate that the HOMO‐LUMO energy gap, the dipole moment, and the electrostatic potential serve as robust descriptors of the inhibitory activity exhibited by 2,3‐dihydroxybenzoyl hydrazine derivative ligands against urease. The ligand designated BH‐k emerged as the most efficacious urease inhibitor, with critical hydrogen bonds forming between it and the residues His409, Ala636, and Asp633, in addition to hydrophobic interactions with Arg439. The design of ligands capable of establishing additional hydrogen bonds constitutes an effective strategy to amplify inhibitory efficacy. The results of this research aspire to lay a theoretical foundation for the advancement of novel urease inhibitor designs to counteract health issues emanating from aberrant urease activity.

Exploration of thiazine Schiff bases as promising urease inhibitors: Design, synthesis, enzyme inhibition, kinetic analysis, ADME/T evaluation, and molecular docking studies

Urease catalyzes the hydrolysis of urea, leading to an increase in stomach pH and supporting Helicobacter pylori survival, which is linked to several gastrointestinal disorders. In this study, thiazine-based Schiff bases were explored as promising urease inhibitors. Various spectroscopic techniques characterized the synthetic library of thiazine Schiff bases 2–36 and also evaluated for their inhibitory activities against urease. The derivatives demonstrated significant inhibitory potential with IC50 values ranging from 0.14 ± 0.08 to 3.66 ± 0.21 μM, outperforming the standard inhibitor thiourea (IC50 = 19.43 ± 0.18 μM). Structure-activity relationship (SAR) studies revealed that specific substitutions (type and positions) on the aryl ring significantly affect the inhibition potential. The most potent derivative, compound 7, possessed 2-methoxy-5-trifluoromethyl substitutions and exhibited an IC50 of 0.14 ± 0.08 μM. Enzyme kinetics studies revealed that the most potent derivatives function as competitive inhibitors. Additionally, molecular docking studies provided insights into the binding interactions between the molecule and the urease active site, highlighting key residues involved in inhibitor binding. These findings highlight the therapeutic potential of thiazine-based Schiff bases as urease inhibitors and provide insights for the development of new anti-ulcer agents.

In silico DFT and molecular modeling of novel pyrazine-bearing thiazolidinone hybrids derivatives: elucidating invitro anti-cancer and urease inhibitors.

In the present work, one of the leading health issues i.e.cancer was targeted by synthesizing and biologically investigating the potential of pyrazine-based thiazolidinone derivatives (1-13). The basic structure of the synthesized compounds was determined using a variety of spectroscopic techniques, including 1H NMR, 13C NMR, and HREI-MS. These scaffolds were studied for their biological profiles as anti-cancer as well as anti-urease agents. The biological effectiveness of these compounds was compared using the reference tetrandrine (IC50=4.50±0.20 µM) and thiourea (IC50=5.10±0.10 µM), respectively. Among novel compounds, scaffold 3, 6, 7 and 10 demonstrated an excellent potency with highest inhibitory potential (IC50=1.70±0.10 and 1.30±0.20 µM), (IC50=4.20±0.10 and 5.10±0.30 µM), (IC50=2.10±0.10 and 3.20±0.20 µM) and (IC50=2.70±0.20 and 4.20±0.20 µM), respectively, out of which scaffold 3 emerged as the leading compound due to the presence of highly reactive-CF3 moiety which interacts via hydrogen bonding. Molecular docking investigations of the potent compounds was also carried out which revealed the binding interactions of ligands with the active sites of enzyme. Moreover, the electronic properties, nucleophilic and electrophilic sited of the lead compounds were also studied under density functional theory (DFT).

Construction of the technological process and design development of a multifunctional unit for processing vital soybeans with ultrasound. Feasibility of water-crude suspension

Cereals and legumes have a porous structure, being an inert carrier during mass exchange processes; they contain voids in the form of pores and stomata, on the surface of which there are foreign extractable substances in a solid state, in particular, trypsin and urease inhibitor proteins. These substances, due to their harmful effect on the final product, are subject to removal by extraction. One of the methods for inactivating anti-nutritional substances is ultrasonic treatment of soybeans.The article discusses the technology of inactivating inhibitors that worsen food and protein value of vital soybeans. The developed technology was aimed at dissolving a solid substance - soybean inhibitor protein in a liquid, carried out due to molecular diffusion, intensifying the processes of mass transfer and mass return. When creating a suspension by mixing the solid (crushed soybean grain) and liquid (water) phases, water molecules, which are a solvent, penetrate under the action of capillary forces into the pores and stomata of the treated body, begin to penetrate. On this basis, technological directions of research have been established, a sequence has been built and the physical essence of operations has been substantiated, consisting of four main ones - grinding soybean grain, creating a “water-soybean” suspension, ultrasonic (US) treatment of soybeans, drying. As a result of the conducted research, optimal technological parameters have been established for intensifying the process of inactivation of anti-nutritional substances contained in native soybeans: the degree of grinding of soybean grains is 0.5-1.0 mm; the ratio of water-soy suspension (1:1). The efficiency of the developed technological process will be factors affecting the quality of the resulting products, the duration and energy intensity of the process, resource conservation, simplicity of design and low cost of manufacture, the possibility of automation.