Three various pyrazine-oxadiazole hybrids 4a-c , 7a-c , and 10a-c were synthesized by reacting the precursor, 4-(pyrazin-2-ylamino)benzohydrazide ( 2 ), with different substituted benzoic acids, aryl isothiocyanates, where the produced thiosemicarbazides cyclized with iodine/NaOH, or aromatic aldehydes, followed by heating the produced hydrazones with acetic anhydride. The scrutinized compounds exhibited analogous planar optimized structures, except for the methoxyphenyl hybrids 4b and 7b, along with the acetyl derivatives 10a-c, which deviated from planarity. The frontier molecular orbitals (FMO) plots of analogues 4a-c and 7a-c revealed a comparable distribution of their highest occupied molecular orbital (HOMO), whereas their Lowest unoccupied molecular orbital (LOMO)s have an alternative structure. As well, from the in vitro anti-tumor activity against three human cancer cells, hybrid 10b displayed a significant activity against HT-29 and Michigan cancer foundation-7 (MCF-7, breast cancer cell line) cells (IC 50 = 15.26±0.28 and 14.62±0.20 µM, respectively). However, hybrid 7b showed superior effectiveness towards MCF-7 cells (IC 50 = 22.57±0.48 µM). Besides, the synthesized hybrids were evaluated for their binding affinity with the human topoisomerase (PDB: 4OLE). Hybrids 7a , 7c , and 10a demonstrated high binding scores (S = -6.6199, -6.2440, and -6.0356 kcal/mol), respectively. Finally, the estimated pharmacokinetic profiles using the Swiss absorption, distribution, metabolism and excretion (ADME) online program were performed and showed that hybrids 7c and 10c exhibited enhanced polar surface areas but reduced their blood–brain barrier (BBB) permeability, emphasizing the balance between hydrophilicity and lipophilicity through the drug’s construction. These discoveries establish the hybrids’ potential as an anticancer drug while providing insights into their physicochemical and ADME profiles.
A magnetically responsive metal-organic framework (MOF) composite, CoFe 2 O 4 @UiO-66-NH 2 , was synthesized via a solvothermal strategy and applied for efficient adsorption of U(VI) from aqueous solutions. The integration of CoFe 2 O 4 nanoparticles within the UiO-66-NH 2 framework enabled rapid magnetic separation while preserving the material’s high surface area and active functional groups. The composite exhibited a maximum U(VI) adsorption capacity of 193.99 mg·g -1 and followed pseudo-second-order kinetics and Langmuir adsorption behavior, with performance reproducible across replicates. The thermodynamic parameters confirmed the process to be spontaneous and endothermic. Mechanistic insights were obtained through X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) calculations. Binding energy analyses revealed that uranyl ions interact primarily with amino and oxygen-containing groups, especially at Zr-O-C and -NH 2 sites. DFT simulations further confirmed the favorable coordination via strong inner-sphere complexation. This work demonstrates a rational approach to designing magnetically separable MOF-based adsorbents with defined molecular-level binding mechanisms, offering promising potential for practical uranium remediation.
Water pollution is a pressing global concern that persists, especially with ongoing population growth. Herein, magnesium oxide/titanium dioxide (MgO/TiO₂) (MgTi1), 2.5% vanadium (V) oxide (V₂O₅)@MgO/TiO₂ (MgTi2), 5% V₂O₅@MgO/TiO₂ (MgTi3), and 10% V₂O₅@MgO/TiO₂ (MgTi4) nanocomposites were prepared as environmentally friendly adsorbents for the removal of the basic fuchsine dye (BFD). The prepared MgTi1, MgTi2, MgTi3, and MgTi4 showed size ranges of (7.7-34.9), (3.1-22.9), (3.9-23.1), and (6.3-27.2) nm, respectively, and surface areas of 170.54, 235.38, 211.86, and 175.25 m 2 g -1 , yielding q t values of 124.2, 238.6, 215.48, and 213.8 mg g -1 , respectively. BFD sorption onto MgTi-based nanocomposites followed the pseudo-second-order model, indicating interactions between sorbent and sorbate, as well as sorbate-sorbate. At 20°C, the BFD sorption by the MgTi2 followed the Langmuir model, while at 50°C, the BFD sorption showed better agreement with the Freundlich model. The thermodynamic analysis showed that the elimination of BFD by MgTi2 was endothermic and spontaneous. The use of MgTi2 as the optimal sorbent for removing BFD from the groundwater and seawater samples demonstrated average efficiencies of 98.92% and 94.04%, respectively. An investigation into the regeneration and reusability of MgTi2 over 5 cycles revealed an average efficiency of 96.4%, indicating that MgTi2 is an effective and economically viable sorbent for the remediation of BFD-contaminated wastewater.
To investigate the impact of ammonia incorporation on the propagation characteristics of methane explosions in the coal mine, the explosion pressure and flame propagation characteristics of methane/ammonia/air mixtures under different ammonia-to-methane mass ratios, initial pressures, and initial temperatures are studied. The results show that the explosion pressure is first decreases and then increases with the increasing of the ammonia-to-methane mass ratio. Meanwhile, the flame position and flame propagation velocity gradually increase. With increasing initial pressure, the peak explosion overpressure, flame propagation velocity, and flame propagation distance all increase. The influence of initial temperature is non-monotonic. When the initial temperature increases from 300 to 700 K, the explosion overpressure rises, and the flame-front propagation trajectory shows a strong positive correlation with temperature. However, the flame propagation is markedly suppressed, as evidenced by a substantial reduction in both the flame-front propagation distance and propagation velocity for T 0 = 900 K. The results from this work can provide insights into the mixed gas explosion and energy utilization.
Esophageal squamous cell carcinoma (ESCC) is characterized by poor therapeutic response and frequent chemoresistance, in which tumor microenvironment-mediated mechanisms play a critical role. Cancer-associated fibroblasts (CAFs) have been implicated in cisplatin resistance through the secretion of quiescin sulfhydryl oxidase 1 (QSOX1), which may contribute to the upregulation of multidrug resistance-associated genes such as ATP-binding cassette subfamily B member 1 (ABCB1, also known as P-glycoprotein, P-gp). In addition, dysregulated iron ion homeostasis within the tumor microenvironment highlights the need for multifunctional therapeutic strategies. Herein, a multifunctional nanoplatform (ALG-1-ATPMS@CP1@Cur) was developed to integrate targeted drug delivery with tumor microenvironment modulation. In vitro studies demonstrated that CAF-derived conditioned medium attenuated cisplatin-induced cytotoxicity in ESCC cells, whereas modulation of CAF signaling by Cur-loaded nanoparticles effectively restored drug sensitivity. Mechanistically, the nanoplatform significantly suppressed QSOX1 expression in CAFs and reduced ABCB1 expression in ESCC cells, suggesting a potential CAF–QSOX1–ABCB1 axis involved in chemoresistance. Furthermore, the nanoplatform exhibited pH-responsive drug release behavior and intrinsic Fe 3 ⁺ sensing capability, providing an auxiliary function for monitoring tumor microenvironment-related biochemical changes.
Despite abietane diterpenoids exhibit various biological activities, their anti-fibrotic activity has rarely been investigated. In the study, 19 diterpenoids (twelve abietanes and seven other types) were isolated from E. helioscopia , comprising five undescribed ent -abietane type diterpenoids ( 1a , 1b , and 2−4 ). Among them, (+)-euphonane A ( 1a ) and (−)-euphonane A ( 1b ) represent previously unreported ent -abietane enantiomers. The structures of unreported diterpenes were mainly assigned through comprehensive nuclear magnetic resonance (NMR) data analysis, in combination with computational techniques involving NMR and electronic circular dichroism (ECD) calculations. In addition, single crystal diffraction analysis precisely defined the absolute stereochemistry of euphonane C ( 3 ). The effect of these 19 diterpenoids to inhibit fibronectin (FN) expression was evaluated in transforming growth factor-β (TGF-β1)-stimulated human hepatic stellate cell line (LX-2 cells), and three compounds ( 1a , 1b , and 3 ) showed significant inhibitory activity at micromolar level, being stronger than the positive control silymarin. A dose-dependent suppression of fibrotic marker expression, particularly that of FN, collagen I, and α-smooth muscle actin (α-SMA), was observed upon the treatment with compounds 1a and 1b . Mechanistic investigations, including transcriptomics analysis and western blotting, revealed that the anti-fibrotic action of 1b in hepatic cells is probably mediated through the TGF-β/Smad signaling cascade. The above results both extend our knowledge regarding the bioactivities of diterpenes isolated from E. helioscopia , and position abietane-type diterpenoids as prospective molecular structures for the innovation of new therapeutics against liver fibrosis.
The research on the mechanical properties of agricultural straw fiber modified cement waste soil aims to explore the deficiencies in the mechanical performance of cement soil when using waste soil as raw material and its potential hazards. As a commonly used building material, the mechanical properties of cement soil are influenced by various factors, especially when waste soil is used, problems such as insufficient strength and poor compressive resistance often occur. Waste soil contains a large amount of unstable substances, which can easily lead to the expansion, cracking and long-term strength reduction of cement soil, thereby affecting the quality and safety of the project. To improve the mechanical properties of cement soil, the study proposes to add agricultural straw fibers for modification. Agricultural straw fiber, as a natural fiber material, have excellent reinforcing effects and can effectively improve the tensile strength, toughness and stability of cement soil. According to the study, agricultural straw fiber cement-stabilized waste soil (FCS) samples' unconfined compressive strength (UCS) first rises and then falls as the amount of agricultural straw fiber increases, peaking at 1%. An appropriate amount of fiber (1%) significantly enhances the stiffness of the soil, while excessive fiber (1.5%) may introduce additional pores and weaken the material's stiffness. The Maximum dynamic shear modulus ( G max ) of FCS samples shows a trend of first increasing and then decreasing with the increase of agricultural straw fiber content. The synergistic effect of fibers and confining pressure is obvious, and the samples with 1% fiber content perform best under high confining pressure, indicating that fibers and confining pressure jointly improve the shear stiffness of the matrix. An appropriate amount of straw fibers can significantly improve the mechanical properties of cement soil and reduce the negative impact of waste soil on the structure of cement soil. Thus, agricultural straw fibers' modification effect offers a fresh concept for using waste soil as a resource and crucial technical assistance for boosting the mechanical qualities of cement soil and project quality.
Y6 and PTB7-Th are widely used acceptor and donor materials in high-efficiency organic solar cells; however, their binary blends are known to suffer from poor long-term morphological stability. Here, we provide a molecular-level explanation for this instability using a systematic density functional theory (DFT) conformational analysis of heterogeneous (PTB7-Th/Y6) and homogeneous (Y6/Y6 and PTB7-Th/PTB7-Th) molecular pairings. Geometry optimizations and binding energy calculations were performed using B3LYP and long-range corrected CAM-B3LYP methods with the 6-31G(d) basis set, with explicit consideration of side-chain effects. A stepwise optimization strategy, progressing from individual sub-units to half-molecules and full molecular assemblies was employed. The results reveal that PTB7-Th homo-pairs exhibit the strongest intermolecular binding, followed by PTB7-Th/Y6 hetero-pairs, while Y6/Y6 interactions are comparatively weak. This hierarchy of binding energies per atom (with typical values of ∼2.2 eV for hetero-pairs and ∼1.9 eV for the average of homo-pairs) indicates that PTB7-Th/Y6 binary blends are intrinsically prone to excessive miscibility and morphological instability, consistent with experimental observations that favor ternary blend architectures. Importantly, we demonstrate that sub-unit interaction analysis reliably predicts the stability and preferred geometry of full molecular systems, establishing a transferable computational framework for assessing donor–acceptor compatibility in organic solar cells.
The current study focused on designing and synthesis of new thiophene-thiazole and bi-thiophene derivatives and evaluate their potential as anticancer agents and carbonic anhydrase inhibitors through experimental and computational investigations. The structure of manufactured thiophene-thiazole and bi-thiophene compounds have been elucidated from the NMR, FTIR, and mass spectral data. The DFT/B3LYP optimized structures of the chloroacetamides 3a-b were planar, whereas the oxothiazolidinylidene analogs 4a-b as well as thiophene carboxamides 7-13 showed a comparable strongly twisted structures. The frontier molecular orbitals (FMOs) of the planar conjugates 3a-b were spread over the full skeleton, while the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of twisted hybrids have been confined to the planar π-aromatic system (substituted phenyldiazenyl thiophene moiety) and the various acceptor functionals, respectively. Furthermore, the cytotoxicity efficiency of the constructed analogues has investigated versus three human cancer cell lines and a normal fibroblast line, where the analogues 7 , 9a , 11 , 13a , and 13b showed higher cytotoxic efficacy than the reference doxorubicin, demonstrating the potential these scaffolds as lead structures for the development of antitumor drugs. Also, the carbonic anhydrase inhibition studies revealed potent activity against the tumor-associated isoforms CA IX and CA XII, with hybrids 9a , 9b , 11 , and 13b showing the strongest dual inhibition (IC 50 = 0.049±0.006 - 0.350±0.036 μM for CA IX and 0.103±0.029 - 0.822±0.003 μM for CA XII). Meanwhile, molecular docking against the CA active site (PDB: 1ZXM) supported the experimental findings, with compounds 9a , 11 , and 13a displaying higher binding affinities than the reference Aza (-5.78 to -7.54 kcal/mol). In addition, SwissADME analysis further indicated favorable pharmacokinetic properties for several derivatives, particularly 9a , 9b , 13a , and 13b . Collectively, the results highlight bi-thiophene-based derivatives as promising leads for the development of carbonic anhydrase-targeted anticancer agents.
Polymer based nanocomposites have emerged as a versatile and efficient class of materials for gas sensing technologies due to their unique combination of flexibility, tunable properties, and cost effectiveness. This review presents a comprehensive overview of the synthesis, structural characteristics, and operational mechanisms of polymer nanocomposites-based gas sensors. Flexible and low-power sensing platforms are crucial for air pollution monitoring. Polymer-based nanocomposites present a promising alternative to traditional gas sensors, especially metal oxide (MO) systems, as they operate at room temperature and offer mechanical flexibility and adjustable surface chemistry. Electrospinning has emerged as a highly effective technique for producing nanofibrous structures that enhance gas sensing due to their large surface area and improved gas diffusion. The addition of functional nanofillers to electrospun polymer matrices further improves detection sensitivity, selectivity, and charge transfer. The impact of key electrospinning parameters, includes polymer concentration, surface tension, solution conductivity, and environmental influences like relative humidity. It elaborates on various gas sensing mechanisms, detailing their principles and material compatibility. Recent advancements in conjugated polymers are also highlighted, particularly in hybrid nanostructures with metal oxides and carbon-based nanomaterials to improve sensitivity, selectivity, and stability. This review also explores the real-world applications in environmental monitoring, medical diagnostics, and volatile organic compound (VOC) detection, along with analysis and challenges including humidity interference, stability issues, and field deployment. Overall, this review work underlines the immense potential of polymer nanocomposites as next generation gas sensing materials and identifies future research directions for optimizing their performance in practical applications.
A series of thiazolo[5,4-b]pyridine–based sulfonamide derivatives was designed and synthesized using a cyanoacetyl sulfonamide intermediate to access various heterocyclic frameworks. Their antimicrobial activity was evaluated in vitro against Staphylococcus aureus , Escherichia coli , and Candida albicans using agar diffusion and minimum inhibitory concentration (MIC) determination. Several compounds exhibited potent antibacterial activity with MIC values ranging from 3.125 to 12.5 μg/mL, where compounds 10 , 16 , and 21 showed broad-spectrum activity comparable to or superior to reference drugs. Structure–activity relationship (SAR) analysis indicated that electron-withdrawing and aromatic substituents enhanced antimicrobial potency. Molecular docking studies against dihydrofolate reductase (DHFR, PDB ID: 2W9S) supported the experimental results, revealing favorable binding interactions and high affinity of the most active compounds. These findings suggest that thiazolo[5,4-b]pyridine–sulfonamide hybrids represent promising scaffolds for the development of new antimicrobial agents.
Tin-related defects and cation disorder are critical factors that limit the performance of Cu 2 ZnSn(S,Se) 4 (CZTSSe) thin-film solar cells (TFSCs) Partial substitution of Sn with Ge has been identified as an effective approach to suppressing antisite defects and reducing open-circuit voltage deficit ( V OC,def ). However, high-concentration Ge doping can have adverse effects on device performance. In this study, we employed an environmentally friendly n-butylammonium butyrate–based solution method to optimize the CZTSSe absorber layers and the resulting solar cells by introducing low-concentration Ge doping, where the atomic ratio of Ge/(Ge+Sn) was varied from 0 to 0.2. The crystal structure, surface morphology, roughness, and elemental chemical states of the films were systematically characterized by using X-ray diffractometer (XRD), scanning electron microscope (SEM), atomic force microscope (AFM), and X-ray photoelectron spectroscopy (XPS). Defect state distribution and carrier recombination mechanisms were further investigated using Raman spectroscopy, temperature-dependent admittance spectroscopy (T-AS), and temperature-dependent open-circuit voltage measurements. The optoelectronic performance of the devices was comprehensively evaluated through J – V measurements, electrical impedance spectroscopy (EIS), and external quantum efficiency (EQE) tests. The results demonstrated that low-concentration Ge doping effectively promotes the growth of large-grain layer, reduces surface roughness, widens the bandgap, and significantly suppresses [2Cu Zn + Sn Zn ] defect clusters and band-tail states, thereby reducing non-radiative recombination losses in both the bulk and at the interfaces. These synergistic improvements collectively enhance the carrier lifetime (τ EIS ), open-circuit voltage ( V OC ), short-circuit current density ( J SC ), and fill factor (FF). The optimal device, with a Ge doping ratio of 15%, achieved a maximum power conversion efficiency (PCE) of 8.65%. This work confirms that low-concentration Ge doping is an effective strategy for enhancing the performance of CZTSSe solar cells and provides important experimental insights into defect control.
The cycloaddition of 1,2,7-triazaspiro[4.4]non-2-en-6-one and the dipole 1-benzylidyne-2-phenyl-1,4,2-diazane is described in this work using density functional theory (DFT) methods. The reaction is found to be both chemoselective and regioselective, and the underlying mechanisms are discussed. Furthermore, an in silico approach was employed to examine the pharmacokinetic profiles, drug-likeness, and potential suitability of P1 derivatives as central nervous system (CNS)-active candidates, particularly in the context of Alzheimer’s disease. Based on the prediction of activity spectra for substances (PASS) model, we estimated the biological activity spectrum of analyzed compounds elucidating their strong neuroprotective and anti-inflammatory potential. Docking studies on MAPK-activated protein kinase 2 (MK-2) and acetylcholinesterase (AChE) targets showed that ligand-target complexes were stable, indicating potential strong inhibitory activity of the P1 derivatives. Pharmacokinetic profiling and BOILED-Egg plot analysis revealed good oral absorption, while P1, P1-F, and P1-Cl showed predicted blood–brain barrier (BBB) permeability, suggesting their potential as CNS-targeted agents. Conversely, P1-NH₂ showed good oral bioavailability but lower BBB permeation and was predicted to be substrate of the P-glycoprotein suggesting that structural modifications should be obviously needed in order to optimize its brain distribution. These results lay down a strong background for further experimental investigation and in vitro/in vivo activity of P1 analogs in the search for new therapies against neurodegenerative diseases.
A series of novel energetic compounds bearing nitrogen-containing aromatic rings, synthesized through energetic methylene bridging, were prepared for the first time. By tuning the bonding sites, the energy levels of these energetic compounds were enhanced while their stability was maintained-their densities range from 1.80 g·cm⁻ 3 to 1.89 g·cm⁻ 3 , and their detonation velocities range from 8000 m·s -1 to 8800 m·s -1 . The resultant energetic materials were fully characterized by Fourier transform infrared (FTIR) spectroscopy, NMR, and X-ray diffraction (XRD). Distinctive properties were observed in crystal structure analysis and differential scanning calorimetry (DSC) tests. Moreover, the energy levels and sensitivity of these compounds were comprehensively evaluated. These novel materials exhibit excellent performance, suggesting potential applications in propellants and composite explosives.
The present work describes the synthesis, molecular docking, and preliminary anticancer evaluation of a hybrid compound, product- C composed of a fluorinated sulfur heterocyclic core and an adamantane moiety. The synthesis method was designed to tune the electronic, lipophilic and structural properties of the compound through the introduction of CF₃, F and Cl functional groups, which are well known for the improving metabolic stability, physicochemical properties and drug-likeness. The structure of the synthesized compound was confirmed by 1 H and 13 C nuclear magnetic resonance (NMR) spectra. Molecular docking against phosphoinositide 3-kinase (PI3K), a protein target implicated in multiple cancers, showed that product- C exhibited a binding affinity of -10.6 kcal/mol, suggesting favorable interaction with the target. In parallel, the SRB (Sulforhodamine B) assay was used to evaluate the cytotoxicity of product- C toward PANC-1 cells. Preliminary results showed cell viabilities of 98.86% and 95.55% after exposure to 10 μM and 100 μM of product- C , respectively. These findings indicate that product- C displays low cytotoxicity toward PANC-1 cells under the tested conditions; however, they do not by themselves demonstrate marked antiproliferative activity.
Ni-doped Cu₂O nanomaterials, using cuprous oxide as a template, have been successfully prepared into Ni(OH)₂/Ni(OOH) doped Cu 2 O@CuO shell-shell nanomaterials through a novel photochemical deposition-etching technique. Under photochemical circumstances, part of Cu 2 O was oxidized to CuO, and nickel hydroxide was deposited on the CuO surface through photochemical reaction. Some nickel hydroxide was oxidized to high-state Ni(OOH), which had higher oxygen evolution reaction (OER) activity than Ni(OH) 2 . The Ni(OH) 2 /Ni(OOH) nanoflakes-doped Cu 2 O@CuO nanomaterial exhibited higher catalytic activity than pure Cu 2 O crystals. The fabrication mechanism of Ni(OH) 2 -Ni(OOH) doped Cu 2 O@CuO core-shell was studied. The surface area of Ni(OH) 2 -Ni(OOH) doped Cu 2 O@CuO core-shell nanomaterials is ten times higher than that of pure Cu 2 O nanocrystals. The Ni(OH) 2 /Ni(OOH)- doped Cu 2 O@CuO core-shell nanomaterials exhibit the highest catalytic activity at a ratio of 10. The possible mechanism of OER on the Ni(OH) 2 /Ni(OOH) modified Cu 2 O@CuO has been elaborated. The Ni(OH) 2 /Ni(OOH)@Cu 2 O has great potential to act as a catalyst for hydrogen production.
The decolorization process of Scutellaria baicalensis polysaccharide (SBP) by macroporous resin was optimized through response surface methodology. The crude SBP (SBP-C) and decolorized SBP (SBP-D) were then structurally characterized by UV, high performance liquid chromatography (HPLC), gel-permeation chromatography (GPC), Fourier transform infrared spectrometer (FTIR), NMR, scanning electron microscopy (SEM), zeta potential, particle size, and thermogravimetric analysis. Their functional properties were evaluated in vitro and by fluorescence spectroscopy, with correlation analysis used to reveal the structure-activity relationship. The results showed that HPD-600 resin exhibited the best decolorization effect under optimal conditions: temperature 38°C, resin dosage 8 g, pH 3.4, and time 2.9 h. After decolorization, the total sugar content and the levels of glucose/arabinose/galactose increased significantly ( p < 0.05), while protein content decreased ( p < 0.05). Low molecular weight polysaccharides (3600–3300 g/mol) were retained, showing a predominantly multi-helical α / β -(1→4) structure with good thermal stability. Particle size and zeta potential decreased by 32.26% and 52.36%, respectively, and the microstructure transitioned into looser sheet-like helical stacks with elevated methyl-esterified galacturonic acid. These alterations improved water stability, moisture absorption, water/oil holding capacity, good emulsifying ability, and enhanced antioxidant and hypoglycemic activities. The IC₅₀ values for scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals and for inhibiting α -amylase and α -glucosidase were 0.19, 0.25, 0.73, and 0.24 mg/mL, respectively. Fluorescence spectroscopy indicated that SBP non-competitively inhibited α -glucosidase and α -amylase via static quenching, with SBP-D showing enhanced efficacy. The preferred decolorization process serves as a promising purification strategy to obtain SBP with desirable functional properties, making it a potential candidate ingredient for functional foods, nutritional products, and other health-related applications.
Promoted by the well-established, valuable biological activity of thiophene-based hybrids, the study displayed the synthesis of two series of thiophene-pyrazole hybrids, 7a-c and thiophene-pyridine hybrids 9a-c, via reacting arylhydrazone with halogenated reagents and nucleophilic addition of cyanoacetamide to the arylidene-malononitrile, respectively. The chemical structure of the produced hybrids was elucidated using reliable spectroscopic techniques, including Fourier transform infrared (FTIR), Nuclear magnetic resonance (NMR), and Mass spectra (MS). The density functional theory (DFT) modeling of the delivered conjugates disclosed comparable non-planar configurations and frontier molecular orbital (FMO) constructions, in which the benzoate junction and oxo-thienyl moiety performed as donor (highest occupied molecular orbital; HOMO) and acceptor (lowest unoccupied molecular orbital; LUMO) portions, respectively. Furthermore, the antimicrobial activity of the manufactured hybrids was evaluated, and analog 7a exhibited outstanding activity against both bacterial strains and C. albicans, with large inhibition zones (IZ = 41-43 mm). Meanwhile, the cytotoxicity efficacy of the synthesized derivatives was assessed against human breast cancer (MCF-7), normal kidney epithelial (Vero), and the normal cells (WI-38) cell lines. The series 7a-c was more active in general than the other conjugates; for example, derivative 7a was very selective towards MCF-7 (IC 50 = 14.39±0.26 μM). Furthermore, the hybrid’s inhibitory effect on the bacterial topoisomerases IV and DNA gyrase B was evaluated, where hybrid 7a presented the greatest action (IC 50 = 12.09±0.31 and 0.43±0.12 μM), respectively. Moreover, molecular docking performed against bacterial DNA gyrase B revealed that analogues 7a-c and 9a-c exhibited superior bindings; analogue 9c demonstrated the strongest binding energy (-7.9520 kcal/mol), proposing improved target arrangement. Finally, the Swiss absorption, distribution, metabolism and excretion (ADME) analysis highlighted the pharmacokinetic properties of the synthesized thiophene hybrids. Analogues with low molecular weight, 4 and 5 , exhibited optimal solubility and absorption, while bulkier analogues 6 , 7a-c, and 9a-c presented lower solubility due to increased topological polar surface area (TPSA) and lipophilicity.
Liver fibrosis, driven by excessive extracellular matrix deposition and hepatic stellate cell (HSC) activation, remains a major clinical challenge. Here, we developed a multifunctional chitosan-based nanozyme ( 1-CS@vitexin ) by integrating the natural flavonoid vitexin into a nitrogen-coordinated framework. The composite exhibits multi-enzyme-mimicking activities (oxidase-, catalase-, and peroxidase-like) that efficiently regulate reactive oxygen species (ROS) and maintain catalytic stability under acidic conditions. Moreover, 1-CS@vitexin shows strong NIR-II absorption and a high photothermal conversion efficiency (η = 52%), achieving stable light-to-heat transformation. In vitro , 1-CS@vitexin significantly inhibited TGF-β1–induced HSC activation, reduced ACTA2, TGFB1, and COL1A1 expression, and suppressed IL-6 secretion. These findings demonstrate that 1-CS@vitexin synergistically modulates oxidative stress, fibrosis, and inflammation, offering a promising catalytic–photothermal platform for effective liver fibrosis therapy.
A series of novel pyridazine-thiazole compounds 6 , 7 , 9 , and 10 were synthesized by introducing various thiazole ring systems into the precursor 4-(pyridazin-3-yl)amino)benzohydrazide compound 4 . The DFT/B3LYP optimized structures of the synthesized hybrids exhibited a non-planar geometry. Frontier orbital structures of the studied derivatives were strongly influenced by structural modifications. For example, in the ester 3 and hydrazide 4 analogues, the HOMO was localized on the phenylamino-pyridazine, whereas the LUMO was mainly centered on the cyano-pyridazine moiety. While in the thiosemicarbazide hybrid 5 , the HOMO has shifted toward sulfur- and nitrogen-rich regions, indicating enhanced intramolecular charge-transfer character. The in vitro cytotoxic activity of the synthesized analogues against HepG2, HT-29, MCF-7, and WI-38 cell lines showed that analogue 10b exhibited potent activity (IC₅₀ = 22.39 ±0.16 μM) against HepG2, while analogue 8 disclosed the good activity toward HT-29, (IC₅₀ = 16.54 ±0.38 μM) and analogue 10a revealed proper efficacy (IC₅₀ = 16.44±0.31 μM) against MCF-7 higher than that of the reference doxorubicin. Besides, the carbonic anhydrase enzymes inhibitory potential against the tumor-related isoforms (CA IX and CA XII) presented hybrids 5 , 7a , 10a , and 10c as good CA IX inhibitors, comparable to the reference inhibitor acetazolamide (AZA). Meanwhile, docking with human 5FL4 protein revealed that the pyridazine-hydrazinyl analogues displayed proper bindings due to their more separate electron density and effective interactions. The pharmacokinetics SwissADME in silico studies indicated that the low molecular weight conjugates respect Lipinski’s rule of five, with optimal value of lipophilicity (iLOGP < 3.27), and exhibit blood-brain barrier permeability. While bulky derivatives showed a reduced gastrointestinal absorption (GI) absorption with increased molecular weight, topological polar surface area.
