Urease is a virulence factor associated with Helicobacter pylori infections, catheter-associated urinary tract infections, and incontinence associated dermatitis. Currently, few treatment options are available to treat urease-positive infections. Acetohydroxamic acid is the only licensed urease inhibitor, licensed in the USA under the name Lithostat. Nasturtium officinale (watercress) is a member of the Brassicaceae family. It has various potential medicinal properties which are little explored. In this study, its potential utility as a treatment option for urease-positive infections was tested. Various compounds present within N. officinale extract are potential urease inhibitors: In vitro, the ability of N. officinale extract to prevent accumulation of ammonia produced in Proteus mirabilis cultures was studied with two potential therapeutic mechanisms identified: 1. Inhibition of the urease enzyme, preventing the production of ammonia; 2. Sequestration of ammonia by isothiocyanates. Putative evidence of activity, in terms of protection of skin barrier function, was obtained in an in vivo human model, where the N. officinale extract was potentially able to prevent erythema caused by ammonia irritation. Finally in silico docking experiments were performed to investigate the binding of compounds found within N. officinale to H. pylori bacterial urease. The anti-inflammatory and antiureolytic properties of N. officinale extract could be utilized as a treatment against urease-positive infections.

Hydrazone compounds and their nickel(II) and cadmium(II) complexes have interesting biological activities. To explore new and efficient urease inhibitors, in this work an aroylhydrazone compound N'-(2-Hydroxy-4-methoxybenzylidene)-4-methylbenzohydrazide (HL) and two complexes [Ni2L2(CH3OH)2(OH2)2]Cl2·2CH3OH (1) and [Cd2L2(CH3COO)2] (2) have been prepared and characterized by elemental analysis, infrared and electronic spectroscopy, as well as single crystal X-ray determination. In addition, 1H and 13C NMR spectroscopy was used for HL. Both complexes are dinuclear compounds. The Ni atoms in complex 1 are in octahedral coordination, and the Cd atoms in complex 2 are in square pyramidal coordination. The Cl- in 1 acts as a counter anion, while the NO3- in 2 coordinates to the metal atoms with bidentate form. The urease inhibitory assay reveals that HL has weak activity, while complexes 1 and 2 have IC50 values of 18.2 ± 1.1 μmol L-1 and 0.38 ± 0.12 μmol L-1, respectively. Both complexes have higher activity than the standard drug acetohydroxamic acid (IC50 = 28.1 μmol L-1).

Urease is a nickel-dependent metalloenzyme that catalyzes urea hydrolysis, generating ammonia and elevating local pH, a process implicated in the pathogenesis of Helicobacter pylori-associated peptic ulcer disease (PUD). To identify effective urease inhibitors, acetohydroxamic acid (AHA) remains the only FDA-approved agent, with clinical use constrained by toxicity. This review synthesizes current evidence on urease inhibition strategies, encompassing metal-based complexes, organic derivatives, natural products, peptide inhibitors, nanotechnology-enabled systems, and emerging gene-based approaches. Several candidates, including copper-based compounds and the natural alkaloid palmatine (PAL), demonstrate potent urease inhibition and favorable effects in preclinical models. However, translation to clinical practice is limited by safety concerns, instability, and a paucity of human trials. Advancing hybrid molecules, optimized delivery platforms, and combination therapies may enhance therapeutic efficacy. Rigorous clinical evaluation remains essential to establish urease inhibition as a viable strategy in urease-mediated diseases.

The dermal exposure to persistent nerve agents such as VX may lead to skin penetration and uptake in the circulatory system. So far, the efficacy of decontamination lotions to remove VX from the skin has been investigated in vitro using methods for transdermal drug delivery systems such as the vertical diffusion cell, which suffer from several disadvantages. We assessed a full thickness model of human skin placed in inserts of 6-well plates to investigate the efficacy of decontaminants to remove VX. Six different decontamination lotions (reactive skin decontamination lotion (RSDL), the potassium salt of the acetohydroxamic acid (AHAK), sodium hypochlorite (NaOCl) 2% and 10%, soapy water 2% and tap water) were evaluated by calculating the amount of VX that penetrated over 300 min. In addition, the impact of the initiation of decontamination (5 min versus 30 min) was investigated. Early decontamination of VX with AHAK was very effective resulting in a complete decontamination. RSDL and NaOCl 2% showed a substantial decontamination efficacy and the penetrated amount of VX was reduced by 88% (RSDL) and 84% (NaOCl 2%). In contrast, the decontamination efficacy of soapy water and tap water was significantly lower. The delayed decontamination was less effective but still the amount of penetrated VX was significantly reduced. In conclusion, the results underline that the full thickness model of human skin is a suitable tool for investigating the decontamination efficacy of various decontaminants. In addition, the model benefits from low technical requirements.

Electrochemical oxidation of ethanol can simultaneously produce hydrogen and value-added acetate, but accurate quantification of acetate in ethanol-rich, high-ionic-strength alkaline electrolytes remains challenging. Here, we report a cost-effective, sensitive UV-Vis spectrophotometric method for acetate determination based on carbodiimide-mediated derivatization: acetate is activated by N,N'-dicyclohexylcarbodiimide (DCC), converted to acetohydroxamic acid (AHA) by NH2OH HCl, and the resulting hydroxamate(s) are detected as chromogenic Fe[3+]-AHA complexes with a maximum at 505 nm. Reaction stoichiometry and temperature were optimized (0.1 mol L[-1] NH2OH HCl, 0.4 mol L[-1] DCC, 0.3 mol L[-1] Fe[3+], 60 °C) to maximize sensitivity and stability. Under these conditions, the assay exhibits a limit of detection of 6.27 × 10[-5] mol L[-1] and a limit of quantification of 1.90 × 10[-4] mol L[-1], with excellent linearity in the tested range. The method shows negligible interference from ethanol across typical sample concentrations in a pH range of 5-8 and tolerates acetaldehyde up to approximately twice the molar concentration of acetate; the derivatized signal remains stable for 120 min. Validation with electrolytes produced by ethanol electro-oxidation on Ni foam yielded acetate concentrations of 12.54, 35.94, 55.58 and 68.49 mmol L[-1] and combined faradaic efficiencies above 94%, demonstrating practical applicability. This DCC→AHA→Fe[3+] UV-Vis assay provides a simple, inexpensive, and robust approach for routine quantitative analysis of acetate in challenging, ethanol-rich alkaline matrices and is readily adaptable for laboratory studies of electrocatalytic ethanol oxidation.

Novichoks are the latest known and most toxic class of organophosphorus chemical warfare agents (OP CWAs) to have been developed. Among the documented Novichoks, A-232 is the most toxic and most potent inhibitor of AChE, as well as the most resistant to reactivation by oximes, and thus likely the most challenging to treat. Here we characterize the intoxication following dermal exposure to the Novichok A-232 in swine, and describe a novel countermeasure against it. Our results demonstrate that percutaneous poisoning by a lethal dose of A-232 (2 mg/kg) is characterized by slow appearance and exacerbation of intoxication signs. We further show that conventional antidotal treatment against such poisoning, administered upon appearance of intoxication signs, provides only temporary relief after which intoxication signs reoccur, and that further repeated such treatment is not sufficient to enable survival. The above likely stem from formation of a dermal depot of A-232 from which the agent slowly penetrates into the bloodstream, coupled with its resistance to reactivation by oximes. Accordingly, we developed the AHAK lotion (potassium acetohydroxamate in DMSO/H2O, derived from the FDA approved medication acetohydroxamic acid (AHA)), intended to act as a 'catch-up therapy' enabling both skin surface and intradermal decomposition of persistent low-volatility OP CWAs. We demonstrate that combining conventional antidotal treatment with dermal application of AHAK following percutaneous poisoning by a lethal dose of A-232, leads to survival of all animals. Additionally, using a low dose (0.33-0.41 mg/kg) of A-232, we show that AHAK is expected to exert a beneficial effect also following late application. Hence, the results of the current study, coupled with our previous results regarding the contribution of AHAK to countering percutaneous intoxication by VX and the safety of prolonged whole-body application of AHAK, delineate the aptness of AHAK to serve as a generic medical countermeasure against percutaneous intoxication by persistent low-volatility OP CWAs, of both the V and Novichok families.

The phenolic compound profile of ethanolic extract of Stropharia inuncta (Fr.) Quél., a natural macrofungus species, and the effects of this chemical structure on antioxidant, anticholinesterase and antiproliferative activities were evaluated. Antioxidant capacity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and Rel Assay Diagnostics kits; DPPH: 72.653 ± 1.857 mg Trolox equivalents (TE)/g, FRAP: 86.873 ± 1.125 mg TE/g, otal antioxidant status (TAS): 4.049 ± 0.057 mmol/L, total oxidant status (TOS): 9.642 ± 0.038 μmol/L, oxidative stress index (OSI): 0.238 ± 0.002, respectively. Within the scope of anticholinesterase activity, IC50 values of the extract on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were determined as 55.007 ± 1.411 μg/mL and 82.993 ± 1.501 μg/mL, respectively. Antiproliferative effect was evaluated on A549 human lung adenocarcinoma cell line after 24 h of incubation; significant decrease in cell viability was observed especially at concentrations of 100 and 200 μg/mL. Phenolic content was analyzed by LC-MS/MS method and the highest levels of gallic acid (3713.45 ± 12.26 mg/kg), quercetin (2911.40 ± 6.19 mg/kg), and 4-hydroxybenzoic acid (2167.69 ± 4.71 mg/kg) were detected. Also compounds such as vanillic acid, catechinhydrate and acetohydroxamic acid were found at significant levels. The findings show that S. inuncta is a rich natural source of phenolic compounds and this chemical structure contributes to versatile biological activities. The limited information in the literature on the biological activities and phenolic compound profile of this species positions the study as a contribution to the field.

The recent use of low volatile nerve agents for assassination attempts has shown that nerve agent poisoning is an ongoing challenge. Immediate decontamination of exposed patients is crucial to prevent systemic effects from skin exposure and to facilitate survival. Currently used skin models to study penetration rates rely on animal or human skin, that has most often been stored in a frozen state (obvious impairement of epidermal tight junction barrier in frozen thawed skin). Thus, we investigated a bioartificial three-dimensional model of human skin which allows the study of decontamination procedures on viable skin. In the Franz diffusion cell, we investigated the effectiveness of different decontamination lotions (RSDL; AHAK; sodium hypochlorite 2% and tap water) by calculating the amount of penetrated VX in the acceptor chamber over 5 h, as a surrogate parameter of decontamination efficacy. The FDA approved RSDL (Reactive Skin Decontamination Lotion) and the AHAK lotion (potassium salt of the acetohydroxamic acid) showed a substantial decontamination efficacy. The penetrated amount of VX in the acceptor chamber (Franz diffusion cell) after 5 h was reduced by 99.97% for AHAK and by 96.57% for RSDL. Sodium hypochlorite (2%) and tap water showed a significantly lower efficacy compared to the lipophilic decontamination agents (RSDL and AHAK). AHAK was also tested as application prior to exposure and showed substantial results. In summary, the results demonstrate that the FT (full-thickness) skin model is a suitable model for investigating the decontamination efficacy of various decontamination solutions against the highly toxic nerve agent VX.

We here report a novel acetohydroxamic acid-assisted peptide hydrazide ligation (APHL) strategy for chemical protein synthesis. With acetohydroxamic acid serving as a non-thiol additive, sodium nitrite-activated peptide hydrazides are in situ converted to reactive peptide O-acyl hydroxamates, which undergo efficient and direct ligation with N-terminal cysteine-containing peptides. This thiol-additive-free approach is compatible with one-pot ligation-desulfurization and ligation-oxidative folding. The utility of this strategy is demonstrated by the expedient synthesis of site-specifically lactylated histone H3 (H3K18la) and the disulfide-rich neurotoxin Calciseptine. Our study expands the repertoire of hydrazide-based ligation and provides a practical, operationally straightforward tool to accelerate chemical protein synthesis.

Dual inhibition of urease and α-glucosidase offers a unified approach to gastric and metabolic disorders. Two new 1,2,4-triazole - Schiff base hybrids (5a, 5b) were designed, synthesized, and spectroscopically verified. Frontier orbitals and electronic descriptors were computed at the B3LYP/6-311++G(d,p) level. Enzyme inhibition was quantified in vitro and rationalized by in-silico docking. Both ligands were potent urease inhibitors: 5a IC50 = 18.63 ± 1.47 μg/mL and 5b IC50 = 16.94 ± 1.09 μg/mL; 5b approached thiourea (14.42 ± 1.13 μg/mL) and surpassed acetohydroxamic acid (19.35 ± 0.94 μg/mL). Against α-glucosidase, 5b showed strong activity (IC50 = 13.78 ± 0.89 μg/mL), comparable to acarbose (11.08 ± 0.85 μg/mL), whereas 5a was moderate (19.66 ± 2.08 μg/mL). Docking corroborated these trends, indicating higher urease affinities for 5a (-7.0 kcal/mol) and 5b (-7.6 kcal/mol) than thiourea (-3.3 kcal/mol), and favorable α-glucosidase binding (-6.2/-6.5 kcal/mol) relative to acarbose (-5.3 kcal/mol). Interaction analyses revealed hydrogen-bond networks, π-π stacking, π-cation/anion contacts, and hydrophobic stabilization; phenolic substituents in 5b reinforced active-site complementarity. By integrating spectroscopy, quantum-chemical characterization, enzyme assays, and docking, this work identifies 5a and especially 5b as multifunctional scaffolds for dual urease and α-glucosidase inhibition with potential utility against Helicobacter pylori-associated gastric disease and type 2 diabetes.

The instability of zinc (Zn) anodes in aqueous electrolytes presents a major obstacle to the widespread commercial use of Zn-ion batteries owing to irreversible reactions and sluggish desolvation kinetics of the electrolyte. This study introduces a novel additive to improve Zn anodes using acetohydroxamic acid (AHA) in a conventional ZnSO4 (ZSO) electrolyte system to optimize the Zn[2+] diffusion behavior and desolvation kinetics, thus promoting uniform Zn deposition on the metallic Zn surface. Both experimental and theoretical calculations demonstrate that AHA molecules tend to replace H2O molecules and attach to the Zn anode, thereby mitigating side reactions and dendrite formation. Consequently, the Zn||Zn symmetric cells with the AHA additive achieve a stable cycle life of 2995 h at 1 mA cm[-2] and endured extremely high current densities of 8 mA cm[-2] for over 1000 h. The Cu||Zn asymmetric cells stabilized over 2100 cycles with an average Coulombic efficiency of 99.3%. The full cell configuration using the NH4V4O10||Zn system exhibits an improved performance, with a capacity retention of 81.9% after 700 cycles at a current density of 5 A g[-1]. This study underscores the importance of AHA additives in regulating Zn anodes to enhance the lifespan of Zn-ion batteries.