Search Results (502)

The escalating crisis of bacterial antimicrobial resistance necessitates the discovery of novel antibacterial agents with distinct mechanisms of action. Ursolic acid (UA), a naturally abundant pentacyclic triterpenoid, serves as a promising scaffold for structural modification. In this study, a series of 26 novel UA derivatives (A1–A7 and B1–B19) were designed and synthesized by introducing various substituents at the C-28 carboxyl group via a chloroacetyl chloride linker. Their antibacterial activities were evaluated against S. aureus, S. epidermidis, E. coli, and P. aeruginosa using the microbroth dilution method. Among them, compound B1 exhibited the most potent activity, with a minimum inhibitory concentration (MIC) of 37.5 μg/mL against S. aureus and 75 μg/mL against E. coli. Antibacterial kinetic and time-kill curve assays confirmed the sustained bactericidal effect of B1. Furthermore, B1 significantly inhibited biofilm formation in both S. aureus and E. coli in a time-dependent manner. Molecular docking studies revealed that B1 binds spontaneously to the S. aureus SarA protein through three hydrogen bonds and π-π stacking interactions, providing a structural basis for its antibacterial and anti-biofilm activities. This study demonstrates that piperazine-modified UA derivative B1 is a promising antibacterial candidate and offers a new strategy for the structural optimization of ursolic acid. Full article

Pseudomonas aeruginosa is a predominant spoilage organism in meat products. The extensive use of antimicrobial preservatives has, however, led to the emergence of resistant strains. Mitigating the resistance of foodborne P. aeruginosa to conventional preservatives has become a critical challenge in food safety. Piperonylpiperazine (Pip), a piperazine derivative sourced from Piper nigrum, was first examined in this work as a novel agent capable of both suppressing virulence and enhancing preservative efficacy against P. aeruginosa, with its mode of action elucidated. At sub-inhibitory concentrations, Pip strongly suppressed the production of virulence factors and potentiated the susceptibility of P. aeruginosa to the common preservative EDTA. Mechanistically, a multi-pronged approach involving pull-down assay, transcriptomic profiling, isothermal titration calorimetry (ITC) analysis, and gene knockout models demonstrated that Pip binds specifically to the LYS-164 and ASP-35 residues of the RhlI synthase, blocking the quorum sensing (QS) signaling cascade. This QS disruption led to reduced virulence factor production and attenuated pathogenicity in a Caenorhabditis elegans model. The compromised QS system subsequently induced oxidative stress, which disrupted cell membrane integrity and permeability, thereby potentiating EDTA’s antibacterial action. These findings suggest that Pip is a promising natural additive that can be used in combination with existing preservatives to enhance food safety. Full article

A previous study identified [¹¹C]M503-1619 as a lead compound for positron emission tomography (PET) radiotracer development. The goal of the current study was to conduct a structure–activity relationship (SAR) study on M503-1619 to improve its in vitro binding affinity for alpha synuclein (aSyn), as well as to identify potential radiotracers that could be labeled with fluorine-18. The results of the SAR study identified strict SARs regarding the introduction of a fluorine into the N-aryl piperazine and benzamide moieties. The most promising compound was the corresponding 2-fluoroethyl analog of M503-1619. This compound was radiolabeled with fluorine-18, followed by in vivo PET imaging studies on non-human primate and in vitro autoradiography study. In vitro autoradiography studies in human postmortem brain sections demonstrated that ¹⁸F-labeled radiotracer has higher binding to synucleinopathies versus control brain tissues. This radiotracer displays the high initial brain uptake and rapid washout that is needed for a PET radiotracer for imaging a protein such as aSyn that has a low target density in the brain. However, the formation of brain penetrant radiolabeled metabolites prevented further evaluation of this compound. Insights from this SAR study are guiding the development of novel aSyn radioligands that avoid formation of the undesirable radiolabeled metabolite. Full article

The remediation of contaminants of emerging concern (CECs) requires innovative, high-efficiency, and sustainable technologies. Here, we investigate active polymeric membranes incorporating TiO₂/ZnO heterojunctions for synergistic sono-enhanced photocatalytic water treatment under both UV and visible-light irradiation. TiO₂/ZnO composites were synthesized and characterized, confirming the formation of type II heterojunctions with tailored optical properties for sunlight-driven photocatalysis. The catalysts were integrated into poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) matrixes using electrospinning (ES) and thermally induced phase separation (TIPS). ES membranes, specifically the ZnO-rich heterojunction within a PVDF-TrFE matrix (3T-7Z@TrFE ES), achieved the highest performance toward ciprofloxacin (CIP) degradation, reaching 71 and 57% under UV and visible light, respectively. The hybridization of the method by coupling ultrasound induced significant synergistic effects, with relative enhancement factors up to 1.38. Furthermore, the sono-enhanced photocatalytic pathway shifted the degradation mechanism towards the early fragmentation of the harmful piperazine ring, yielding a more sustainable degradation process. In addition, the composite membranes showed selective antibacterial activity against S. aureus, making this a multifunctional platform able not only to degrade CECs but also to mitigate membrane fouling. Overall, this work demonstrates the potential of tailored heterojunctions and composite membranes as sustainable platforms for the remediation of recalcitrant CECs in water, highlighting the synergy between photoactivity, piezoelectricity, and mechanistic control. Full article

Ferroptosis has emerged as a critical mechanism linking iron dysregulation, oxidative stress, and neurodegeneration in amyloid-associated pathologies. Building on our previous work, which identified compound 20 as a promising antioxidant and neuroprotective agent, the present study investigates the molecular mechanisms underlying its protective activity against amyloid-induced ferroptosis in human neuroblastoma SH-SY5Y cells exposed to Aβ(25–35). Compound 20 (3-(((4-hydroxybenzyl)(methyl)amino)methyl)-1-methyl-N-(2-(piperazin-1-yl)ethyl)-1H-indole-5-carboxamide) markedly counteracted Aβ(25–35)-induced ferroptotic damage by restoring intracellular glutathione levels, depleting the labile iron pool, and suppressing lipid peroxidation. In parallel, the compound significantly rescued mitochondrial membrane potential and attenuated endoplasmic reticulum (ER) expansion associated with ER stress, thereby preserving cellular homeostasis under oxidative challenge. These protective effects were further corroborated by real-time PCR analysis, which revealed the modulation of key genes involved in the oxidative stress response, endoplasmic reticulum stress, and inflammatory pathways. To gain a systems-level insight into these mechanisms, untargeted ¹H-NMR metabolomic profiling was performed. This analysis confirmed the activation of antioxidant pathways and disclosed a significant modulation of energy metabolism and GABA-related pathways, both of which are closely linked to redox balance and neuronal resilience. Overall, these findings demonstrate that compound 20 drives metabolic reprogramming that orchestrates its multifactorial protective effect against Aβ(25–35)-induced ferroptosis by coordinating antioxidant defense, iron homeostasis, and ER stress mitigation. Full article

Chemical absorption is currently the most mature technology for carbon capture from flue gas in coal-fired power plants. The selection of the amine solution system and process optimization directly determine the energy consumption of carbon capture and are critical to the large-scale implementation of the amine process. In this study, a composite amine solution of N-methyl-diethanolamine-piperazine-water (MDEA-PZ-H₂O) was selected as the CO₂ absorbent. Aspen HYSYS (14.0) software was used to establish a typical process model for CO₂ capture from flue gas in coal-fired power plants. Using single-factor sensitivity analysis, key process parameters in the typical carbon capture process—including amine solution composition, flue gas inlet temperature, lean liquid temperature, and gas-to-liquid ratio—were optimized. Based on the process optimization, this study conducted integrated energy-saving optimization by optimizing the temperature distribution in the absorption tower (achieved through the integration of inter-stage cooling in the absorption tower) and regeneration energy savings (achieved through the coupling of the Mechanical Vapor Recompression (MVR) process). The results indicate that the carbon capture system integrating the inter-stage cooling process with the MVR energy-saving process reduces the energy consumption per unit of carbon captured by 15.15% compared to a typical process system. This demonstrates that the integration of multiple energy-saving processes with the recovery of flue gas and CO₂ waste heat recovery within the system is an effective approach to reducing the energy consumption per unit of carbon capture. Full article

This research paper focused on the synthesis of 1-[2-hydroxy-3-(phenylcarbamoyloxy)propyl]-4-(R¹, R²-substituted phenyl)piperazin-1-ium chlorides (I)–(III), containing R¹, R² = H, Cl and/or OCH₃, and the evaluation of some of their physicochemical parameters. The in vitro biological investigation of these N-arylpiperazine (NAP) derivatives consisted in assessing their impact on purinergic P2X7-associated signaling, that is, the evaluation of antioxidant, anti-inflammatory and immunomodulatory characteristics. The ultraviolet type C (UVC) irradiation (λ = 254 nm, 0.954 kJ/m²) induced a pronounced stress response in human leukocytes without marked cytotoxicity while maintaining high cell viability (≥90%), as evidenced by increased interleukin (IL)-1β production (94%), elevated IL-1β mRNA expression, enhanced lipid peroxidation (66%), and increased intracellular adenosine 5′-triphosphate (ATP; 97%), respectively. Under basal conditions, these lipophilic NAPs, defined with logarithmic values of retention (capacity) factors corresponding to 100% water in isocratic elution RP-HPLC, i.e., k_w descriptors (varying from 2.3829 to 4.3689), and isocratic chromatographic hydrophobicity index (φ₀) parameters (ranging from 0.7578 to 0.8842), reduced IL-1β production (by 26–63%) and enhanced superoxide dismutase (SOD) activity (up to 64%) without inducing oxidative damage. Under UVC-induced stress, all evaluated compounds decreased lipid peroxidation (up to 45%) and significantly increased antioxidant enzyme activities, including SOD (up to 223%) as well as catalase (up to 145%). The observed effects were associated with changes in intracellular ATP levels and redox-related parameters. In the experiments described in this paper, intracellular ATP was measured so that no direct conclusions could be drawn regarding the extracellular ATP-dependent activation of purinergic receptors, including P2X7. Overall, the results demonstrated that variations within the structure of these NAPs significantly affected compounds’ biological activity, highlighting their potential for further optimization as cytoprotective and anti-inflammatory agents. Full article

PVP-stabilized silver nanoparticles (Ag NPs) were functionalized with sildenafil (Sil), leading to spherical NPs (Ag@Sil NPs) with a size of about 30 nm as observed through transmission electron microscopy and dynamic light scattering. Fourier-transformed IR spectroscopy confirmed the covering of the particles with Sil. The Ag@Sil NPs were incorporated into a 0.1 wt% ointment and tested for the treatment of acute anal fissures in a preliminary medical study involving 50 patients. Typical symptoms such as pain, bleeding, itching, and mass sensation were improved in the intervention group with no adverse effects. Molecular docking showed strong interactions with docking scores slightly above −10 kcal/mol between sildenafil and two different model complexes [Ag–Sil]⁺ for the Ag-bound sildenafil with either piperazine-N- or pyrazole-N-bound Ag⁺ ions and the muscarinic M2 and the nicotinic acetylcholine α3β4 receptor, which are both involved in anal sphincter regulation. All three showed superior binding compared with nitroglycerin and L-arginine. The residue analysis revealed a higher number of relevant interactions for the sildenafil and the two Ag⁺ complexes, compared to nitroglycerin and L-arginine, fully in line with the differences in the docking scores. Full article

Wood’s inherent flammability, arising from its cellular organic composition, demands effective protective strategies. This study aimed to develop a multifunctional bio-based wood coating simultaneously integrating flame retardancy, optical transparency, moisture-triggered self-healing, and surface hydrophobicity within a single formulation. An intumescent flame retardant (PAGHR) was synthesized via ionic assembly of a phytic acid–phosphorylated polyethylene glycol conjugate (PgP) with a piperazine–etidronic acid salt (HEPHR), subsequently blended with gelatin (G) and surface-finished with fluorosilane. The optimized coating (G/PAGHR-4) achieved a limiting oxygen index (LOI) of 37.2% and passed the UL-94 V-0 rating. Cone calorimetry demonstrated reductions of 75.1% in peak heat release rate (pHRR) and 50.0% in total heat release (THR) relative to the neat gelatin control. Char yield at 700 °C increased substantially from 17.8 wt% to 41.0 wt%, confirming effective condensed-phase char promotion. Beyond fire performance, the coating maintained high visible-light transmittance, preserved natural wood aesthetics, and achieved macroscopic scratch healing within 40 min upon ambient water contact. Fluorosilane finishing elevated the water contact angle to 122°. These results establish a scalable, environmentally friendly strategy for multifunctional bio-based protective coatings applicable to wood, textiles, and polymer substrates. Full article

To address the common drawbacks of polyamine-based CO₂ absorbents, such as high viscosity and precipitation at high CO₂ loading, a novel liquid–liquid biphasic absorbent composed of triethylenetetramine (TETA), 1-(2-aminoethyl)piperazine (AEP), N,N-dimethylacetamide (DMAC), and H₂O was developed in this study. By comprehensively evaluating CO₂ saturation loading, phase separation behavior, rheological properties of the CO₂-rich phase, precipitation suppression, and desorption–regeneration performance, the optimal absorbent formulation was identified as 20 wt% TETA + 10 wt% AEP + 40 wt% DMAC + 30 wt% H₂O. The optimized system enabled more than 98% of the CO₂ absorption products to be concentrated in the lower phase, which accounted for only 56% of the total liquid volume. Compared with the AEP-free TETA/DMAC/H₂O system, the optimized AEP-modified absorbent effectively eliminated precipitation and reduced the viscosity of the CO₂-rich phase to 62.3 mPa·s, while also improving the desorption behavior and cyclic stability of the system. In addition, ¹³C NMR analysis suggested that the salting-out effect is the main driving force for phase separation, with ionic products preferentially enriched in the aqueous phase to form the CO₂-rich lower phase. AEP contributes to viscosity reduction, precipitation suppression, and enhanced regeneration by weakening carbamate aggregation through steric hindrance and promoting bicarbonate formation. Full article

The post-combustion carbon capture process with monoethanolamine/piperazine (MEA/PZ) blends encounters notable modeling and optimization challenges. These arise from strong thermodynamic–kinetic nonlinear coupling, as well as limited availability of high-quality experimental data. To address this, we propose a machine learning and multi-objective optimization strategy driven by physicochemical features. By extracting explicit physical features and embedding physicochemical constraints into data-driven models, this study evaluated the predictive performance of three distinct algorithms based on wet-wall column experimental data. These algorithms included natural gradient boosting (NGBoost), sure independence screening and sparsifying operator (SISSO), and gaussian process regression (GPR). Subsequently, an optimization problem aimed at minimizing $P_{{\mathrm{CO}}_2}^{*}$ and maximizing $k_{\mathrm{g}}^{\prime }$ was formulated. The multi-objective beluga whale optimization (MOBWO) algorithm was then employed for global optimization and benchmarked against the traditional non-dominated sorting genetic algorithm II (NSGA-II). Results indicate that the Gaussian process regression (GPR) model performed best when it was enhanced by physicochemical features and optimized via Bayesian hyperparameter tuning. It achieved R² values of 0.989 and 0.953 for $P_{{\mathrm{CO}}_2}^{*}$ and $k_{\mathrm{g}}^{\prime }$, with average absolute relative deviations (AARDs) kept below 15.7% and 12.2% respectively. Feature importance analysis validated the underlying physical laws. Specifically, temperature dictates thermodynamic equilibrium, while CO₂ loading limits mass transfer kinetics. In the optimization phase, MOBWO outperformed NSGA-II by generating a more uniformly distributed Pareto front. Decision-making analysis further identified three typical operating regimes encompassing kinetics-dominant, thermodynamics-dominant, and comprehensive equilibrium conditions. This framework provides a robust paradigm for small-sample modeling and optimization in complex chemical processes. Full article

In the present work, we synthesize 2-(4-allyl-2-methoxyphenoxy)-1-(4-phenylpiperazin-1-yl)ethan-1-one, a semisynthetic derivative of the natural product eugenol. The compound was synthesized via a three-step synthetic pathway involving esterification, hydrolysis, and subsequent coupling with 4-phenylpiperazine, as confirmed by FTIR, ¹H NMR, ¹³C NMR, and mass spectrometric data. Full article

Background/Objectives: Acute myeloid leukemia (AML) is a hematological malignancy frequently driven by mutations in the FLT3 gene, particularly internal tandem duplications (FLT3-ITD), which contribute to aberrant cell proliferation and resistance to tyrosine kinase inhibitors (FLT3i). The limitations of current FLT3i therapies, including drug resistance, off-target effects, and poor selectivity, necessitate the development of novel therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) represent a promising approach to achieving degradation of oncogenic proteins. Methods: We developed FLT3-targeting PROTACs based on the previously described compound MA49, with a focus on linker modifications to improve degradation efficiency and pharmacokinetic properties. Results: Among these, compounds MA190 and MA191, containing rigid cyclohexyl-piperidine/piperazine linkers, demonstrate superior degradation of FLT3-ITD in MV4-11 AML cells at nanomolar concentrations, achieving >95% reduction in FLT3-ITD levels, outperforming MA49. In addition to improved kinase selectivity, good solubility, and plasma stability, MA190 and MA191 also exhibit excellent metabolic stability, whereas the predecessor PROTAC MA49 was unstable in microsomal assays. In cellular assays, MA190 and MA191 induce potent apoptosis in FLT3-ITD⁺ AML cells but have minimal effects on cells with wild-type FLT3. Proteomics reveal that MA191 also degrades MAPK14 (p38α), a kinase upregulated in leukemia, in addition to FLT3. Conclusions: Dual targeting of FLT3-ITD and MAPK14 enhances proapoptotic signaling without any cytotoxic effect on normal human HEK293 cells. The co-inhibition using MA191 or a combination of doramapimod (a MAPK14 inhibitor) with a non-degrading FLT3 inhibitor result in greater caspase-3 activation than either treatment alone. This synergistic effect can be a therapeutic advantage, as several oncogenic drivers are switched off simultaneously by MA191. Full article

Research on low-concentration CO₂ capture technology is of great significance for China to achieve “carbon peak and carbon neutrality”. However, there are currently two challenges in low-concentration CO₂ capture technology: high energy consumption and significant methane loss. Therefore, in this study, a numerical simulation method is used to establish the reaction model of the piperazine-activated N-methyl diethanolamine (abbreviated as MDEA-PZ) system with CO₂ using Aspen HYSYS industrial software, taking shale gas from a production area as the raw material gas. Single-factor sensitivity analysis is conducted to study the impact of N-methyl diethanolamine (abbreviated as MDEA) mass fraction, piperazine (abbreviated as PZ) mass fraction, CO₂ absorption temperature, and amine liquid regeneration temperature on the process. The results show that when the N-methyl diethanolamine mass fraction is between 37% and 42% and the piperazine mass fraction is between 2.5% and 5%, the regeneration energy consumption is lower and methane loss is smaller. For the raw material gas in this study, the recommended optimal amine liquid mass ratio is 40% of N-methyl diethanolamine + 3% of piperazine. Under this condition, the preferred absorption temperature is 46 °C, the amine liquid circulation rate is 45 m³/h, and the regeneration temperature is 118 °C, resulting in a significant reduction in the total energy consumption by 8.9% compared with the initial value. Full article

Ten compounds have been prepared among them six different dioxido(pyridine-2,6-dicarboxylato)vanadate(V) compounds with piperazinium (H₂pip²⁺) (1·6H₂O), methylpiperazinium (H₂mepip²⁺) (2·5H₂O), ethylpiperazinium (H₂etpip²⁺) (3·3H₂O), isopropylpiperazinium (H₂isopip²⁺) (4·H₂O), phenylpiperazinium (Hphepip⁺) (5∙H₂O) and thiomorpholinium 1-oxide (HtmorO⁺) (6·2,6-H₂pydc·2H₂O) cations as counterions as well as methylpiperazinium (H₂mepip²⁺) salt of a mixed valence vanadium [VO(2,6-pydc)-(μ-O)-VO(H₂O)(2,6-pydc)]⁻ complex (7), thiomorpholin-4-ium vanadate (Htmor)VO₃ (8), hexa(thiomorpholin-4-ium) decavanadate hexahydrate (Htmor)₆[V₁₀O₂₈]·6H₂O (9·6H₂O) and organic salt cocrystal thiomorpholin-4-ium 6-carboxypicolinate pyridine-2,6-dicarboxylic acid (Htmor)⁺(2,6-Hpydc)⁻∙(2,6-H₂pydc)·2H₂O (10·2H₂O) via different pathways starting either from pyridine-2,6-dicarboxylic acid or its esters, and were structurally characterized by single-crystal X-ray diffraction. Extended hydrogen bonding interactions are present due to the presence of organic cations as well as due to the diverse roles of water molecules in the hydrogen bonding network. Centrosymmetric hydrogen bonding was found to be an important motif, and diverse supramolecular patterns were also observed due to a wide variety of C–H···O and π···π interactions stabilizing the crystal lattices. Full article