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The urease enzyme has been an important target for the discovery of effective pharmacological and agricultural products. Thirteen regio-selectively alkylated benzimidazole-2-thione derivatives have been designed to carry the essential features of urease inhibitors. The urease enzyme was isolated from Helicobacter pylori as a recombinant urease utilizing the His-tag method. The isolated enzyme was purified and characterized using chromatographic and FPLC techniques showing a maximal activity of 200 mg/mL. Additionally, the commercial Jack bean urease was purchased and included in this study for comparative and mechanistic investigations. The designed compounds were synthesized and screened for their inhibitory activity against the two ureases. Compound 2 inhibited H. pylori and Jack bean ureases with IC50 values of 0.11; and 0.26 mM; respectively. While compound 5 showed IC50 values of 0.01; and 0.29 mM; respectively. Compounds 2 and 5 were docked against Helicobacter pylori urease (PDB ID: 1E9Y; resolution: 3.00 Å) and exhibited correct binding modes with free energy (ΔG) values of −9.74 and −13.82 kcal mol−1; respectively. Further; the in silico ADMET and toxicity properties of 2 and 5 indicated their general safeties and likeness to be used as drugs. Finally, the compounds’ safety was authenticated by an in vitro cytotoxicity assay against fibroblast cells.

Infection of the human stomach by Helicobacter pylori remains a worldwide problem and greatly contributes to peptic ulcer disease and gastric cancer. Without active intervention approximately 50% of the world population will continue to be infected with this gastric pathogen. Current eradication, called triple therapy, entails a proton-pump inhibitor and two broadband antibiotics, however resistance to either clarithromycin or metronidazole is greater than 25% and rising. Therefore, there is an urgent need for a targeted, high-specificity eradication drug. Gastric infection by H. pylori depends on the expression of a nickel-dependent urease in the cytoplasm of the bacteria. Here, we report the 2.0 Å resolution structure of the 1.1 MDa urease in complex with an inhibitor by cryo-electron microscopy and compare it to a β-mercaptoethanol-inhibited structure at 2.5 Å resolution. The structural information is of sufficient detail to aid in the development of inhibitors with high specificity and affinity. Infection by Helicobacter pylori is associated with peptic ulcers and gastric cancer. H. pylori urease is required for colonization of the stomach and thus an attractive antimicrobial drug target. Cryo-EM analyses of the H. pylori urease with inhibitors bound reveal structural details useful in rational drug design.

Clinically significant problems such as kidney stones and stomach ulcers are linked to the activation of the urease enzyme. At low pH, this enzyme gives an ideal environment to Helicobacter pylori in the stomach which is the cause of gastric ulcers and peptic ulcers. In recent work, we have developed a library of 4-fluorocinnamaldehyde base thiosemicarbazones and assessed them for their potential against urease enzyme. The synthesized compounds displayed significant to moderate inhibition potential with IC 50 values ranging from 2.7 ± 0.5 µM to 29.0 ± 0.5 µM. compound 3c displayed the highest inhibition potential followed by 3a and 3b . Two compounds of the series 3f and 3 g remained inactive against urease. The kinetic study of compound 3c exhibited a competitive type of inhibition with a K i value of 3.26 ± 0.0048 µM. SAR analysis was also thoroughly done. Molecular docking was used to analyze the interaction pattern of each derivative, and the outcomes demonstrated that the compounds had excellent binding interactions with the active site.

Urea is the most popular and widely used nitrogenous fertilizer. High soil urease activity rapidly hydrolyses applied urea to ammonia which contributes to soil nitrogen (N) losses and reduces N use efficiency of crop plants. The ammonia losses can be minimized by the inhibition of soil urease activity which has been explored using various potential chemical inhibitors. However, the soil urease activity inhibition potential of plant extracts is rarely explored to date. In the present study, extracts of 35 plant materials were taken and evaluated against jack bean urease. Eleven extracts, showing >50% jack bean urease inhibition, were selected and further investigated in 13 soils collected from various districts of Punjab, Pakistan. Interestingly, except Capsicum annum , Melia azedarach , Citrus reticulata and Quercus infectoria , the plant extracts showed urease inhibition activities in soils, the extent of which was lower as compared to that observed in jack bean urease though. Maximum urea hydrolysis inhibition (70%) was noted with Vachellia nilotica which was 40% more than that of hydroquinone (50%) followed by that of Eucalyptus camaldulensis (24%). The extracts of V . nilotica and E . camaldulensis were coated on urea and applied to soil in the next step. At 21 st day, 239% and 116% more urea-N was recovered from soil treated with V . nilotica and E . camaldulensis extracts coated urea, respectively, as compared to uncoated urea. Conclusively, these results indicated that the coating of V . nilotica and E . camaldulensis extracts on urea prills prolonged urea persistence in soil owing to minimum urea hydrolysis, probably, the extracts of V . nilotica and E . camaldulensis showed their urease inhibition potential. The results of this study provide a base line for the identification of new soil urease inhibitor compounds from plant materials in future.

In this critical review, plant sources used as effective antibacterial agents against Helicobacter pylori infections are carefully described. The main intrinsic bioactive molecules, responsible for the observed effects are also underlined and their corresponding modes of action specifically highlighted. In addition to traditional uses as herbal remedies, in vitro and in vivo studies focusing on plant extracts and isolated bioactive compounds with anti-H. pylori activity are also critically discussed. Lastly, special attention was also given to plant extracts with urease inhibitory effects, with emphasis on involved modes of action.

The development of new bioactive compounds is important for progress in therapeutic research. In the present study, we describe the multistep synthetic approach to develop a library of novel benzimidazole analogs incorporating piperazine rings in order to increase their biological activity. In order to synthesize the desired benzimidazole analogs, the synthesis started with the easily accessible precursors between aniline and chloroacetyl chloride. It proceeded via a series of reactions, such as condensation, cyclization, and N -alkylation. TLC optimized each step, and spectroscopic methods such as CHN, IR, EIMS, 1 H-NMR, and 13 C-NMR were used to characterize the final products. The urease inhibitory activity of the synthesized compounds was evaluated. It was discovered that almost all compounds were quite effective, even more potent (IC 50  = 0.15–12.17 µ M) than the standard thiourea (IC 50  = 23.11 ± 0.21 µ M). The structure-activity relationship (SAR) is also established, which displayed that compound 9 L (IC 50  = 0.15 ± 0.09 µ M) with -NO 2 substitutions at meta position play a major role in urease inhibition and figure out as the most potent analog of the library. These results were further verified by molecular docking analysis, which indicated favorable binding energies and interactions of the compounds with the urease active site. This study not only depicts the importance of multistep synthesis but also the structure-based modification approach to produce new pharmacophores for therapeutic applications.

This study examines the chemical composition, antioxidant properties, and urease inhibitory effects of Hyoscyamus muticus L. subsp. falezlez (Coss.) Maire. Using LC-ESI-MS/MS, 19 distinct phenolic compounds were identified, with chlorogenic acid being the most abundant. The ethanol extract demonstrated notable antioxidant activity, highlighting its potential for therapeutic use. Urease inhibition assays revealed a remarkable 91.35% inhibition by the H. muticus extract, with an IC50 value of 5.6 ± 1.20 μg/mL, indicating its promising role in addressing conditions linked to urease activity. Molecular docking studies further investigated the interaction between H. muticus phenolic compounds and urease, identifying hyperoside as a leading candidate, with a binding energy of −7.9 kcal/mol. Other compounds, such as rutin, luteolin, apigenin, kaempferol, hesperetin, chlorogenic acid, and rosmarinic acid, also demonstrated significant binding affinities, suggesting their potential to disrupt urease function. These findings highlight the therapeutic potential of H. muticus as a source of natural bioactive compounds, offering promising avenues for the development of novel treatments for urease-related disorders and oxidative stress.

Helicobacter pylori urease is a key virulence factor and a validated target for anti-infective strategies. In this study, a comprehensive computational workflow was applied to identify potential urease inhibitors through a drug repurposing approach. A curated library was first filtered using permeability-related descriptors and multiparametric scoring. The resulting compounds were evaluated through ensemble and consensus docking across multiple protein conformations and docking engines, followed by XP rescoring, metal–ligand distance analysis, and molecular dynamics simulations. Binding stability and thermodynamic profiles were further assessed using MM-GBSA and well-tempered metadynamics. This integrative strategy led to the identification of several candidate compounds exhibiting favorable docking scores, stable coordination with the catalytic Ni2+ center, and consistent binding behavior during molecular dynamics simulations. Notably, selected compounds showed improved relative binding free energy profiles compared to reference inhibitors within the applied computational framework. Overall, this study provides a robust computational pipeline for urease inhibitor identification and highlights repurposed compounds as promising candidates for further experimental validation.

This study reports the plant extract-assisted synthesis of iron oxide (Fe 3 O 4 ) using the aqueous extract of Thevetia peruviana . The synthesized IONPs were confirmed via UV–Vis spectroscopy (295 nm) and characterized using FTIR and SEM. Density Functional Theory (DFT) calculations indicated a thermodynamically and mechanically stable system with semimetallic behavior and visible light absorption. The biological activities of the IONPs were evaluated, including enzyme inhibition assays for urease, α-glucosidase, carbonic anhydrase-II, and xanthine oxidase, as well as anticancer activity. The Fe₃O₄ NPs exhibited potent enzyme inhibition, including urease (94.78%, IC₅₀ = 24.98 µg/mL), α-glucosidase (86.09%), and carbonic anhydrase-II (82.98%, IC₅₀ = 24.78 µg/mL). Additionally, molecular docking was performed to evaluate the interaction of Fe₃O₄ NPs with target enzymes, supporting their inhibitory potential. The NPs also demonstrated notable anticancer activity, particularly against MDR 2780AD (IC₅₀ = 0.39 µg/mL). These results showed significant enzyme inhibition and anticancer properties, indicating the potential of these green-synthesized IONPs in biomedical applications.

A urease inhibitor with good in vivo profile is considered as an alternative agent for treating infections caused by urease-producing bacteria such as Helicobacter pylori. Here, we report a series of N-monosubstituted thioureas, which act as effective urease inhibitors with very low cytotoxicity. One compound (b19) was evaluated in detail and shows promising features for further development as an agent to treat H. pylori caused diseases. Excellent values for the inhibition of b19 against both extracted urease and urease in intact cell were observed, which shows IC 50 values of 0.16 ± 0.05 and 3.86 ± 0.10 µM, being 170- and 44-fold more potent than the clinically used drug AHA, respectively. Docking simulations suggested that the monosubstituted thiourea moiety penetrates urea binding site. In addition, b19 is a rapid and reversible urease inhibitor, and displays nM affinity to urease with very slow dissociation (k off =1.60 × 10 −3  s −1 ) from the catalytic domain.