Search Results (662)

In the present work, a novel series of eleven sulfonate derivatives with potent inhibitory activity against butyrylcholinesterase (BChE) is reported. Of these, compounds 2-[(E)-(2-Benzoylhydrazinylidene)methyl]phenyl 5-(dimethylamino)naphthalene-1-sulfonate (5c, IC₅₀ = 1.11 µM) and tert-butyl (2E)-2-[(2-{[5-(dimethylamino)naphthalene-1-sulfonyl]oxy}phenyl)methylidene]hydrazine-1-carboxylate (5b, IC₅₀ = 11.51 µM) exhibit stronger inhibitory activity than rivastigmine, the reference compound, and exhibit high selectivity for BChE over AChE (e.g., selectivity index 57 for 5c). Interestingly, compound 5c also exhibited anti-inflammatory effects, which is important for potential therapeutic applications, especially in Alzheimer’s disease. These new compounds were designed through a structure-based approach using molecular modeling techniques (docking, molecular dynamic (MD) simulations, and QTAIM (quantum theory of atoms in molecules) calculations). The most promising compounds show no detectable toxic effects and satisfy Lipinski’s rule of five, indicating that they represent attractive starting structures for the design of new derivatives acting as specific BChE inhibitors. In addition, our results indicate that relatively simple computational techniques such as docking calculations and toxicity prediction programs can be valuable when properly used in the search of new candidates for this particular target. Docking calculations show that the more active compounds of this series reach the bottom region of the gorge interacting with residues within the active site of BChE. However, our data further suggest that the use of more precise techniques, such as MD simulations and QTAIM analysis, is necessary to obtain detailed insight into ligand–enzyme interactions. Regarding QTAIM calculations, they demonstrate that such computations are very useful to evaluate the molecular interactions of the different molecular complexes. In summary, we report a new series of sulfonate derivatives as promising starting structures for the development of new selective BChE inhibitors. Full article

Background/Objectives: Antimicrobial resistance (AMR) is an escalating global threat driven by antibiotic misuse and bacterial adaptation. Efflux pumps are major contributors to multidrug resistance in Escherichia coli, as they expel antibiotics and reduce their intracellular activity. This study examined efflux-mediated resistance in extended-spectrum beta-lactamase (ESBL)-producing E. coli and evaluated the potential of several efflux pump inhibitors (EPIs)—promethazine (PMZ), thioridazine (TZ), carbonyl cyanide m-chlorophenyl hydrazine (CCCP), reserpine (RES), and phenyl-arginine-β-naphthylamide (PAβN)—as therapeutic adjuncts. Methods: Antibacterial and anti-biofilm activities of EPIs were tested using broth microdilution, real-time fluorimetry, and crystal violet assays, while ceftriaxone–PMZ interactions were assessed by checkerboard analysis. Results: TZ and CCCP showed strain-specific antibacterial activity, whereas PMZ, RES, and PAβN did not exert any effect. PMZ, TZ, and especially CCCP effectively inhibited efflux pump function, while RES and PAβN were less active. Biofilm inhibition varied between strains, with PMZ and TZ producing moderate reductions. We observed a quite weak synergism between ciprofloxacin, ceftriaxone, and PMZ; however, the result was not significant. Conclusions: Overall, the results highlight the central role of efflux pumps in ESBL-producing E. coli and indicate that EPIs can reverse resistance (e.g., PMZ) and exhibit potent anti-biofilm activity and show additive interactions with antibiotics. However, further studies are needed to optimize their safety, pharmacokinetics, and antibiotic pairing for potential clinical use. Full article

Background/Objectives: Targeting ABL tyrosine kinase (TK) remains a cornerstone of chronic myeloid leukemia (CML) therapy. Methods: In this study, a series of novel 4-((2-(4-(aryl)thiazol-2-yl)hydrazineylidene)methyl)-N,N-diphenylaniline derivatives (1–12) were synthesized through the reaction of 2-(4-(diphenylamino)benzylidene)hydrazine-1-carbothioamide (intermediate A) with substituted 2-bromo-1-arylethanones. Cytotoxic activity was evaluated in K562 CML cells using the MTT assay. The most active compound was further assessed in HL-60 acute myeloid leukemia (AML) cells and healthy peripheral blood mononuclear cells (PBMCs). Apoptosis induction was analyzed by Annexin V/ethidium homodimer staining, while ABL TK inhibition was determined using the ADP-Glo kinase assay. Molecular docking studies were performed to investigate binding interactions within the ATP-binding site of ABL TK, and pharmacokinetic properties were also predicted. Results: Intermediate A demonstrated superior antiproliferative activity compared to derivatives 1–12 and exhibited cytotoxicity comparable to imatinib in K562 cells (IC₅₀ = 6.15 ± 1.26 µM vs. 5.14 ± 1.44 µM, respectively). In HL-60 cells, intermediate A showed an IC₅₀ of 12.04 ± 1.70 µM, similar to imatinib. Notably, intermediate A displayed enhanced selectivity toward K562 cells over PBMCs (SI = 12.9) relative to imatinib (SI = 6.2). The compound significantly induced apoptosis in K562 cells and inhibited ABL TK activity. Docking studies revealed a distinct binding orientation within the ATP-binding pocket of ABL TK. The compound showed acceptable predicted physicochemical and ADME characteristics based on in silico analysis. Conclusions: Intermediate A emerges as a significant anti-CML candidate exhibiting potent cytotoxic, apoptotic, and moderate ABL TK inhibitory activity, together with a favorable selectivity profile. Full article

To identify fungicide lead compounds with novel scaffolds and high efficacy, 33 novel bacillamide–acylhydrazone derivatives were successfully designed and synthesized by using a molecular hybridization strategy. The bioassay results showed that most of the target compounds exhibited promising inhibitory activity against B. cinerea. Among them, compound BAD-15 displayed the most potent antifungal activity with an EC₅₀ value of 6.725 μg/mL. Furthermore, preliminary SAR analysis revealed that the R group in hydrazine fragments exerts a significant influence on antifungal potency. Studying the molecular mechanism by morphological observation and transcriptome analyses revealed that BAD-15 may inhibit the activity of copper ion transmembrane transporters, leading to disrupted copper ion homeostasis and subsequent suppression of fungal growth. The present work indicates that bacillamide–acylhydrazone has potential as a novel scaffold for the development of fungicides, and compound BAD-15 may serve as a potential lead compound for the further development of novel fungicides. Full article

With the increasing deployment of lithium iron phosphate (LiFePO₄) batteries in electric vehicles and energy storage systems, the recycling of these materials has become an urgent necessity. Specifically, the reclamation of lithium iron phosphate cathode materials presents a significant challenge in the recycling process. In this study, we proposed an efficient low-temperature hydrothermal direct regeneration method aimed at repairing lithium vacancies and Fe/Li inversion defects in spent lithium iron phosphate resulting from prolonged cycling. By using this method, spent lithium iron phosphate was successfully regenerated through a hydrothermal process conducted at 80 °C for 6 h, utilizing hydrazine hydrate (N₂H₄·H₂O) as a potent reducing agent and lithium hydroxide (LiOH·H₂O) as the lithium source. X-ray diffraction (XRD) analysis, coupled with Rietveld refinement, revealed a substantial reduction in the concentration of Fe/Li anti-site defects in the spent material, decreasing from 8.8% to 3.3% following regeneration. Consequently, the electrochemical performance was significantly restored. The initial specific discharge capacity increased from 118.0 mAh·g⁻¹ to 150.3 mAh·g⁻¹, and the capacity retention after 100 cycles (at 1 C) improved from 67.5% to 90.7%. The hydrothermal regeneration process introduced in this work effectively repairs the material structure and restores the active valence state of iron, thereby significantly enhancing lithium-ion diffusion and electron transport capabilities. This approach constitutes a technically viable solution for the efficient, environmentally friendly, and cost-effective recycling of spent lithium-ion batteries. Full article

To replace highly toxic hydrazin-driven reaction control systems, a number of non-toxic alternatives are under development. These are usually referred to as “green propellants”. One candidate is the bi-propellant combination of nitrous oxide and hydrocarbons that combine good storability with a comparatively high specific impulse (${\mathrm{I}}_{\mathrm{SP}}$) at a medium to low system complexity level compared to existing hydrazine thrusters. This propellant combination was chosen because of experimentally available results with C₂H₄-N₂O thrusters as validation data. One advantage of this fuel/oxidizer combination is that both gases are self-pressurant and that they can be used as monopropellants at a lower specific impulse ${\mathrm{I}}_{\mathrm{SP}}$ with reduced model complexity. This helps the design of the propulsion system on satellites. A detailed numerical simulation of a representative thruster based on the fuel combination ethylene and nitrous oxide is presented. The numerical model is set up with a suitable kinetic reaction mechanism for the simulation of the reactive mixture in the combustion chamber. It is validated against experimental data available in the literature. Full article

Wound healing is a complex process essential for maintaining skin integrity; however, the rise of antibiotic-resistant bacteria limits therapeutic options, highlighting the critical need for new antimicrobial agents. In this context, this research focused on the synthesis of new azole derivatives and their biological evaluation, specifically targeting antimicrobial, antioxidant, and biocompatible properties relevant to wound infections. In the present work, ketoconazole derivatives were obtained through an initial reaction with an excess of hydrazine hydrate, followed by condensation with benzaldehydes and cyclization with chloroacetyl chloride to form a β-lactam ring. These compounds were evaluated in vitro for antioxidant activity using FRAP, DPPH, and TAC assays, and for antimicrobial activity against a variety of microorganisms. Additionally, the cytotoxicity was assessed using the MTT assay on a normal mouse fibroblast cell line (NCTC, clone L929) for evaluating the biocompatibility of the obtained compounds. Derivative K1 exhibited the highest antioxidant activity, a finding confirmed by all three assays. Regarding antimicrobial properties, all compounds demonstrated notable activity, with K1, K4 and K5 displaying superior efficacy. Significantly, the MTT assay revealed that the derivatives exhibit dose-dependent cytotoxicity but maintain favorable safety profiles at therapeutic concentrations, supporting their suitability for topical application. In conclusion, these findings suggest that the synthesized derivatives may serve as promising leads for infected wound therapy. Future research will further explore the therapeutical potential of these compounds, together with their incorporation into polymeric films designed for chronic wound treatment. Full article

This study presents a straightforward strategy for producing novel, effective and inexpensive functional non-noble metal-supported carbon materials made from abundant natural biomass. These materials offer a cost-effective alternative to noble metals for the oxidation of hydrazine (HzOR) and demonstrate the potential for widespread adoption of green, energy-saving hydrazine-based technologies in energy applications. Highly efficient and cost-effective iron (Fe) and manganese–iron (MnFe)-supported nitrogen-doped carbon (N–C) materials were developed using hydrothermal synthesis. Meanwhile, the N–C material was obtained from biomass—birch-wood chips—using hydrothermal carbonisation (HTC), followed by activation and nitrogen doping of the resulting hydrochar. The morphology, structure, and composition of the MnFe, MnFe/N–C, and Fe/N–C catalysts were determined using scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectroscopy (EDS). The activity of the catalysts for HzOR in an alkaline medium was evaluated using cyclic voltammetry (CV). Depositing MnFe particles onto N–C was shown to significantly enhance electrocatalytic activity for HzOR compared to the Fe/N–C catalyst and especially to the MnFe particles catalyst in terms of highly developed porous structure, which offers the largest surface area, lowest onset potential, and highest current density response, resulting in the strongest catalytic activity. These results suggest that the MnFe/N–C catalyst could be a highly promising anode material for HzOR in direct hydrazine fuel cells (DHFCs). Full article

Background: Among the 15 human (h) carbonic anhydrase (CA; EC 4.2.1.1) isoforms, hCA IX and XII are particularly important due to their roles in tumor cell growth and survival, identifying them as promising targets for anticancer therapy. As a result, considerable effort has been directed toward the development of novel inhibitors that are highly selective for these isoforms. Methods: A library of twelve novel N-aryl-2-(4-sulfamoylphenyl)hydrazine-1-carbothioamides 3 along with two new N-aryl-2-(4-sulfamoylphenyl)hydrazine-1-carboxamide derivatives 5 were synthesized and their inhibition abilities were tested against four human carbonic anhydrase isozymes (hCA I, II, IX and XII) related to some global diseases including glaucoma, cancer and osteoporosis. Results: All compounds exhibited potent inhibition of the tested isoforms in the nanomolar range. Compound 3i showed the highest inhibition of hCA I activity but demonstrated poor selectivity toward the other isoforms. Compound 3h displayed superior selectivity for hCA II over hCA I (hCA I/II = 37) and exhibited 2.5-fold higher inhibitory activity compared to acetazolamide (AAZ). Among the tested compounds, 3l (K_i = 32.1 nM) demonstrated markedly improved selectivity for hCA IX over hCA I, II, and XII relative to the standard drug. Notably, compound 3a showed the most potent inhibition against hCA XII (K_i = 6.8 nM), comparable to AAZ, while exhibiting significantly greater selectivity over off-target isoforms and the other tumor-associated isozyme (hCA IX/XII = 20 versus hCA IX/XII = 4.5 for AAZ). Conclusions: The present study suggests potent lead compounds as selective hCA IX and XII inhibitors with anticancer activity. Full article

Seven amidrazones containing a characteristic NH₂–N=C(Ar¹)–NHAr² moiety, where Ar¹, Ar² are phenyl, 4-methylphenyl, 4-nitrophenyl, 2-pyridyl, and 4-pyridyl substituents, denoted as 2a–2g, were synthesized by the reactions between thioamides and hydrazine. Their molecular structures were confirmed by ¹H, ¹³C, ¹H-¹³C HMQC, ¹H-¹³C HMBC, and ¹H-¹⁵N HMBC NMR spectroscopy, with complete assignment of the detected signals, as well as by high-resolution mass spectra. The biological activity of all compounds was studied, exhibiting antioxidant properties determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods, inhibitory potential against digestive tract enzymes (α-amylase, lipase, pepsin), cytotoxicity (hemolysis), and antimicrobial activities (against Gram-positive and Gram-negative bacteria, and a fungus). The antioxidant activity of the studied amidrazones varied from 83.34% to 93.27% and 1.01–5.79 mM FeSO₄ for the DPPH and FRAP methods, respectively. Moreover, these derivatives revealed inhibition potential against α-amylase (28.6–86.8%), lipase (28.0–60.0%), and pepsin (34.1–76.6%), which increased when increasing their concentrations from 0.2 to 1 mg/mL. Among them, compound 2d (possessing 2-pyridyl and 4-nitrophenyl substituents) stood out in particular, as a potent antioxidant (DPPH = 90.43%, FRAP = 4.73 Mm FeSO₄) with the highest activity against Gram-positive bacteria: S. aureus (MIC = 64 μg/mL), G. rubripertincta (MIC = 64 μg/mL), and fungus: C. albicans (MIC = 32 μg/mL); high α-amylase (86.8%) inhibition at the highest concentration (1 mg/mL); and lipase (38.0%) and pepsin (43.8%) inhibition at the lowest concentration (0.2 mg/mL). The obtained results were analyzed by unsupervised multivariate techniques to confirm significant differences in the biological activity of amidrazones depending on the Ar¹ and Ar² substituents. Full article

Chromium complexes with triamidoamine derivatives bearing bulky substituents at the terminal positions of the ligands, tris(2-(3-pentylamino)ethyl)amine (H₃L^Pen) and tris(2-dicyclohexylmethylaminoethyl)amine (H₃L^Cy), are prepared: [{Cr(L^Pen)}₂(μ-N₂)] (1), [{CrK(L^Pen)(μ-N₂)(Et₂O)}₂] (2), [CrCl(L^Pen)] (3), [Cr(L^Cy)] (4), [CrK(L^Cy)(μ-N₂)(18-crown-6)(THF)] (5(THF)), and [CrCl(L^Cy)] (6). The preparation of these complexes is confirmed by X-ray diffraction analysis. Complexes 1, 2, and 5(THF) have coordinated dinitrogen molecules, with N–N bond lengths of 1.185(3), 1.174(9), and 1.162(3) Å, respectively. These lengths are significantly elongated compared to that of a free dinitrogen molecule (1.10 Å), indicating that the N₂ ligands are activated. The ν(¹⁴N–¹⁴N) values of 1, 2, and 5(THF) are 1715 cm⁻¹ for 1 (Raman, in solution), 1787, 1743 cm⁻¹ for 2 (IR, in solid), and 1824 cm⁻¹ for 5(THF) (IR, in solid), respectively. These values are markedly smaller than free nitrogen (2331 cm⁻¹), confirming that the dinitrogen is interacting with the metal ions and is activated. The structures of 2 and 5(THF) in solution are also studied by ¹H NMR and solution IR spectroscopies. ¹H NMR spectra of these complexes reveal that the peaks of 2 and 5(THF) are observed in the diamagnetic region, whereas those for the other complexes (1, 3, 4, and 6) exhibit paramagnetic shifts. The reactions of these complexes with K[C₁₀H₈] and HOTf under N₂ in THF yield hydrazine and a small amount of ammonia; however, they are not catalytic. The ¹H NMR and IR spectra of the products obtained by reacting 1 or 3 with reductant K in THF under N₂ atmosphere indicate that 2 is formed based on spectral agreement. Similarly, upon examining for 4 or 6, it is confirmed that a species similar to 5(THF) is generated. Full article

Novel pyrrole-based derivatives were synthesized in high purity and yields (52–89%), with 17i and 17j displaying selective MAO-B inhibition (50–60%), comparable to Selegiline, and negligible MAO-A activity. In rat brain subcellular fractions, both compounds showed low intrinsic neurotoxicity at 100 μM while exerting significant neuroprotective and antioxidant effects under 6-OHDA, t-BuOOH, and Fe²⁺/ascorbate-induced stress. Mechanistic studies indicate dual protection via reactive oxygen species scavenging and preservation of reduced glutathione, with mitochondria and microsomes being the most responsive compartments. The performed in silico analysis revealed no general toxicity alerts, though hydrazine groups classify the compounds as contact allergens, and the furan ring in 17i poses hepatotoxic and carcinogenic risks. Metabolic predictions suggest ester hydrolysis at the pyrrole ring as the main biotransformation pathway. Overall, 17i and 17j are promising lead compounds for developing therapeutics targeting oxidative stress-related neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, supporting further in vivo studies. Full article

Defect engineering in semiconductor heterojunctions offers a promising route for enhancing the selectivity of photocatalytic CO₂ conversion. In this work, a ZnS/gel-derived TiO₂ photocatalyst featuring sulfur vacancies introduced via hydrazine hydrate (N₂H₄) treatment is developed. XRD, HRTEM, and XPS analyses confirm the formation of a crystalline heterointerface and a defect-rich ZnS surface, enabling effective interfacial electronic modulation. The optimized ZnS/gel-derived TiO₂-0.48 composite achieves CH₄ and CO yields of 6.76 and 14.47 μmol·g⁻¹·h⁻¹, respectively, with a CH₄ selectivity of 31.8% and an electron selectivity of 65.1%, clearly outperforming pristine TiO₂ and the corresponding single-component catalysts under identical conditions. Photoluminescence quenching, enhanced photocurrent response, and reduced charge-transfer resistance indicate significantly improved interfacial charge separation. Mott–Schottky analysis combined with optical bandgap measurements reveals pronounced interfacial charge redistribution in the composite system. Considering the intrinsic band structure of ZnS and gel-derived TiO₂, a Z-scheme-compatible interfacial charge migration model is proposed, in which photogenerated electrons with strong reductive power are preferentially retained on ZnS, while holes with strong oxidative capability remain on gel-derived TiO₂. This charge migration pathway preserves high redox potentials, facilitating multi-electron CO₂ methanation and water oxidation. Density functional theory calculations further demonstrate that sulfur vacancies stabilize *COOH and *CO intermediates and reduce the energy barrier for *COOH formation from +0.51 eV to +0.21 eV, thereby promoting CO₂ activation and CH₄ formation. These results reveal that sulfur vacancies not only activate CO₂ molecules but also regulate interfacial charge migration behavior. This work provides a synergistic strategy combining defect engineering and interfacial electronic modulation to enhance selectivity and mechanistic understanding in CO₂-to-CH₄ photoconversion. Full article

Organic monosubstituted hydrazine derivatives (Ar-NHNH₂, RC(O)-NHNH₂, Alkyl-NHNH₂) are synthetically available, atom-efficient and stable sources of C-centered radicals upon oxidation with extrusion of the energetically favorable N₂ molecule. This review summarizes the synthetic application of monosubstituted hydrazine derivatives (arylhydrazines, carbazates, acylhydrazides, hydrazine carboxamides and alkylhydrazines) in free-radical C-C bond-forming reactions. The main application directions in this field are (a) alkene difunctionalization, (b) cascade cyclization initiated by the addition of hydrazine-derived C-centered radicals to acrylamides and isonitriles, and (c) CH-functionalization of (hetero)arenes via C-centered radical addition followed by oxidative dehydrogenation (re-aromatization). Full article

This work aimed to synthesize new derivatives of 2-hydrazinylpyridine-3-carbonitrile and to investigate their biological activity as safeners for the 2,4-D herbicide. The new 2-hydrazinylnicotinonitriles were obtained in high yields (up to quantitative) under mild conditions (25 °C, dioxane) by treating 4,6-diaryl-2-bromo-3-cyanopyridines with hydrazine hydrate. The latter were synthesized by brominating 2-(3-oxo-1,3-diarylpropyl)malononitriles, the Michael adducts, which are readily available from 1,3-diarylpropenones (chalcones) and malononitrile. An unusual side product of the bromination/carbocyclization was isolated and characterized; it consisted of co-crystals of 3-benzoyl-4-hydroxy-4-phenyl-2,6-di-(p-tolyl)cyclohexane-1,1-dicarbonitrile and 3-benzoyl-5-bromo-4-hydroxy-4-phenyl-2,6-di-(p-tolyl)cyclohexane-1,1-dicarbonitrile at a ~4:6 ratio. The new 2-hydrazinylnicotinonitriles react with halogen-containing aromatic aldehydes to form the corresponding hydrazones. The biological activity of the new nicotinonitriles was examined for their function as 2,4-D antidotes. It was found that, under laboratory conditions, eight of the synthesized compounds exhibited a notable antidote effect against 2,4-D on sunflower seedlings. Full article