Frontiers in Chemistry最新文献

Background: Artemisia absinthium has long been recognized for its therapeutic properties against various diseases. Among these is leishmaniasis, a parasitic infection that remains a global health challenge. Targeting Leishmania N-myristoyltransferase (NMT), a crucial enzyme for parasite survival, represents a promising therapeutic approach. The bioactive compounds in A. absinthium could potentially inhibit NMT and serve as new treatment options for leishmaniasis.

Aim: This study aims to investigate the phytochemical composition, drug-likeness, and molecular dynamics of A. absinthium bioactive compounds targeting Leishmania NMT, identifying potent inhibitors that could serve as new drug candidates.

Method: The extract of A. absinthium was analyzed using High-Performance Liquid Chromatography (HPLC), identifying nine phenolic compounds, with kaempferol (10.72%) and chlorogenic acid (4.43%) being the most abundant. Drug-likeness and toxicity were evaluated using SwissADME and OSIRIS Property Explorer, focusing on adherence to Lipinski's rule of five and Ghose's filter. Molecular docking studies were conducted to evaluate the binding affinity of these compounds to NMT. Molecular dynamics (MD) simulations were performed to assess the stability and flexibility of the NMT-apigenin complex.

Results: Molecular docking identified apigenin as the most potent NMT inhibitor, with a binding energy of -9.6 kcal/mol, forming significant hydrogen bonds with threonine residues 203 and 189. Drug-likeness analysis revealed that most compounds adhered to Lipinski's rule of five, indicating favorable pharmacokinetic properties. MD simulations confirmed the stability of the NMT-apigenin complex, with root mean square deviation (RMSD) values of 0.04 nm, root mean square fluctuation (RMSF) values between 0.05 and 0.35 nm, and radius of gyration (Rg) values ranging from 2.24 to 2.30 nm. Normal mode analysis further supported the complex's stability and flexibility.

Conclusion: The findings of this study underscore the potential of Artemisia absinthium compounds, particularly apigenin, as promising candidates for the development of new anti-leishmaniasis drugs. The potent inhibition of Leishmania NMT by apigenin, along with its favorable pharmacokinetic and stability profiles, supports its further exploration in antileishmanial drug development.

With the continuous advancement of smart greenhouse technologies, digital and information-based environmental monitoring has emerged as a focal point of research. The development of high-performance gas sensors is central to achieving this objective. In recent years, MXene materials have been widely applied in the field of gas sensors due to their excellent ion mobility, favorable hydrophilicity, outstanding electronic conductivity, and unique physicochemical properties. Various MXene heterojunction structures have been synthesized for gas detection. This review aims to summarize the current state of research on Ti₃C₂T_x-based gas sensors, explore methods for synthesizing different morphologies of Ti₃C₂T_x heterojunction structures, and evaluate the sensing behaviors of these configurations to fully harness their potential for gas monitoring in greenhouse environments. Additionally, an in-depth analysis of the sensing mechanisms associated with Ti₃C₂T_x heterojunction structures will be provided, offering theoretical support for future investigations. The findings indicate that Ti₃C₂T_x-based nanomaterials demonstrate considerable promise as high-performance sensors for gas detection in greenhouse settings. This innovative research not only provides new insights into the development of gas sensor technologies but also serves as an important foundation for the digitization of environmental monitoring.

Introduction: Many beneficial compounds found in fig leaves can be used in tea and medicine. These compounds aid with digestion, reduce inflammation, and treat diabetes and bronchitis. Chetoui, Malha, Ghoudane, and Onk Hmam fig leaf hydro-ethanol extracts from Eastern Morocco were analyzed for metabolites and biological activities.

Methods results and discussion: HPLC-UV examination revealed that the leaf extract included mainly caffeine, rutin, and ferrulic acid. Spectrophometric results show that Malha leaf is rich in polyphenols (62.6 ± 1.3 mg GAE/g) and flavonoids (26.2 ± 0.1 mg QE/g). Chetoui leaf contains the highest vitamin C content (8.2 ± 0.1 mg Asc A/100 g DW), while Onk Hmam leaf has the highest condensed tannin (4.9 ± 0.1 mg CatE/g). The investigations found that all leaf extracts were antioxidant-rich, with strong Pearson bivariate correlation between bioactive polyphenol levels and antioxidant tests for DPPH, β-carotene, ABTS, and TAC (values of -0.93, -0.94, -0.85, and 0.98, respectively). The coefficients for flavonoid content were -0.89, -0.89, -0.97, and 0.80, respectively. Disk diffusion and MIC results show that the hydro-ethanol fig leaf extracts eliminate fungi and bacteria. In addition, these fig leaf extracts showed promise cytotoxicity against the breast cancer cell lines MCF-7, MDA-MB-231, and MDA-MB-436 and an interesting selectivity index. In silico leaf bioactive component analysis revealed that myricitin inhibited NADPH oxidase the greatest (gscore -6.59 Kcal/mol). Trans-ferulic acid inhibits Escherichia coli beta-ketoacyl-[acyl carrier protein] synthase (-6.55 kcal/mol), whereas quercetin inhibits Staphylococcus aureus nucleoside diphosphate kinase (-8.99). CYP51 from Candida albicans is best treated with kaempferol and myricitin. Both had a glide gscore of -7.84 kcal/mol. Rutin has the most potent Sespace 3 anticancer activity, with a glide gscore of -7.09 kcal/mol.

Conclusion: This research indicates that fig leaf extracts from the region can be used in medicine, food, natural cosmetics, and breast cancer prevention. To maximize the value of these leaves, their use must be carefully studied. Naturally, this fortunate tree's diversity must be preserved and enhanced.

Rechargeable aqueous alkaline Zn-Ni batteries (AZNBs) are considered a potential contender for energy storage fields and portable devices due to their inherent safety, high output voltage, high theoretical capacity and environmental friendliness. Despite the facilitated development of AZNBs by many investigations, its practical application is still restricted by inadequate energy density, sluggish kinetics, and poor stability. Therefore, Ni-based cathodes with boosted redox chemistry and enhanced structural integrity is essential for the high-performance AZNBs. Herein, this review focus on critical bottlenecks and effective design strategies of the representative Ni-based cathode materials. Specifically, nanostructured optimization, defect engineering, ion doping, heterostructure regulation and ligand engineering have been employed from the fundamental aspects for high-energy and long-lifespan Ni-based cathodes. Finally, further exploration in failure mechanism, binder-free battery configurations, practical application scenarios, as well as battery recycling are considered as valuable directions for the future development of advanced AZNBs.

Supramolecular gel can be used to seal fractures and pores in the formation during oil and gas drilling and production. In this study, a supramolecular gel plugging agent based on hydrophobic association was prepared by free radical polymerization of acrylamide, octadecyl methacrylate, sodium dodecyl sulfate and other monomers by micellar copolymerization. The forming time, rheology, swelling, mechanical properties and plugging properties of supramolecular gels were studied. The experimental results show that the formation time of supramolecular gel plugging agent is controllable, and it has excellent viscoelastic recovery ability in a certain range of shear strain and scanning frequency. When the compression amount is close to 88.3%, the compressive stress reaches 3.82 MPa. Meanwhile, the swelling performance of supramolecular gel was good, and the equilibrium swelling degree reached 22.1% after 188 min swelling in 15% NaCl brine solution. In 1% NaCl solution, the equilibrium swelling degree of supramolecular gel reached 32.5%. In addition, supramolecular gel has strong formation bonding ability, good plugging performance, plugging rate is greater than 95%, can effectively reduce the leakage and improve the plugging effect of low permeability layer. It is of reference and guiding significance for the long-term plugging of heterogeneous and malignant leakage formations.

Bioluminescent high-throughput screening (HTS) assays, based largely on the activity of firefly (FLuc), Renilla (RLuc), and/or NanoLuc (NLuc) luciferases, are widely utilised in research and drug discovery. In this study, we quantify the luciferase-based real-life HTS assay interference from biologically and environmentally relevant metal ions ubiquitously present in buffers, environmental and biological matrices, and as contaminants in plastics and compound libraries. We also provide insights into the cross-effects of metal ions and other key experimental and biological reagents (e.g., buffer types, EDTA, and glutathione) to inform HTS assay design, validation, and data interpretation. A total of 21 ions were screened in three robust HTS assays ("SC" assays) based on the luminescence of FLuc, RLuc, and NLuc luciferases. Three newly optimised HEPES buffer variants ("H" assays) were developed for direct luciferase comparison. Interference in bioluminescent signal generation was quantified by calculating the IC₅₀ values from concentration-dependent experiments for selected highly active and relevant metal ions. Metal ion inhibition mechanisms were probed by variations in specific reagents, EDTA, GSH, and the sequence of addition and buffer composition. In this study, we revealed a significant impact of metal ions' salts on luciferase-mediated bioluminescence, even at biologically and environmentally relevant concentrations. The extent of signal interference largely aligned with the Irving-Williams series of metal ion-ligand affinities (Cu > Zn > Fe > Mn > Ca > Mg), supporting previous reports on metal ion-dependent FLuc inhibition. However, the absolute magnitude and relative extent of signal reduction by metal ions' salts differed between SC and H assays and between luciferases, suggesting a complex network of metal ions' interactions with enzymes, substrates, reactants, and buffer elements. The diversity of the tested conditions and variability of responses provided insights into potential interference mechanisms and synergies that may exacerbate or alleviate interference. The beneficial influence of EDTA and the impact of glutathione, present natively in cells, on bioluminescence readout were pinpointed. Given the ubiquity of metal ions in analysed samples, the causative role in false-positive generation in drug discovery, and the wide breadth of luciferase-based assays used in screening, awareness and quantification of metal influence are crucial for developing assay validation protocols and ensuring reliable screening data, ultimately increasing the critical robustness of bioluminescence-based HTS assays.

Salami, a well-known fermented meat product, is made from selected ground meat mixed with curing agents and spices. This work aimed to determine the viability of Lactiplantibacillus plantarum (as a starter), Lactobacillus acidophilus (probiotic microorganism), and their mixture during the fermentation and ripening of a salami-type product, evaluate the microbiological and physicochemical changes and assess the sensory acceptability of the final product. L. acidophilus has not been sufficiently explored as a probiotic in fermented meats, especially in terms of its effects on fermentation and sensory qualities. Salami-type products were formulated and fermented for 48 h at 32°C, and then ripening took place at 8°C for 13 days. pH, titratable acidity, Lactobacillus counts, and contaminating microbiota were analyzed during the process. Sensory evaluation was analyzed in the final products. The salami-type formulation served as an effective medium for growing microorganisms, with the populations of starter and probiotic cultures exceeding 10⁸ CFU/g after fermentation and ripening for 15 days. The pH of the end products was ∼5.1, titratable acidity ∼2.5%, and aw ∼0.83. During fermentation and ripening, a significant reduction in total mesophilic aerobic bacteria (>7 logs), coliforms, and Staphylococcus aureus (>8-fold reductions) were observed. The sensory evaluation results indicate that the product's attributes are not influenced by the type of bacteria used, as no significant difference was found (p > 0.05). The results show that L. acidophilus, Lactiplantibacillus plantarum, or their mixture can be used as a starter culture in fermented meat products. Using L. acidophilus, whether alone or in combination, is a viable option that preserves the characteristics of the fermented product and may enhance the benefits of probiotic consumption.

Background: Neisseria gonorrhoeae is the bacterium responsible for gonorrhoea, one of the most common sexually transmitted infections (STIs) globally. In 2020, the World Health Organization (WHO) estimated 82.4 million new cases of Neisseria gonorrhoeae infections. Current treatments rely on antibiotics, but the emergence of multi drug resistance (MDR) strains poses a significant threat to public health. This research aims to use computational modeling of cyclotides as antimicrobial agents targeting the Neisseria gonorrhoeae PorB Porin protein to inhibit its pathogenicity.

Methodology: The PorB Porin protein was retrieved from the Protein Data Bank (PDB ID: 4AUI), cleaned, and visualized using Discovery Visual Studio. Physicochemical properties were predicted using ProtParam. Cyclotides were obtained from the CyBase database, with 3D models generated and refined via the Swiss Model for docking studies. HDOCK was used for molecular docking. Toxicity and allergenicity predictions were performed with ToxinPred and AlgPred. A heatmap of the peptide was created using Protein-Sol. Molecular dynamics (MD) simulations were conducted for 100,000 picoseconds using Desmond from Schrödinger LLC, while binding energy was analyzed using MMGBSA. Immune response simulations were done with C-ImmSim 10.1, and peptide simulation in water was performed via WebGro.

Results: The protein's GRAVY value is -0.539, indicating moderate hydrophilicity, and its isoelectric point is 9.14, suggesting a fundamental nature. Globa D had the highest docking score (-270.04 kcal/mol) and was deemed non-toxic and non-allergenic. MD simulations showed stable protein-ligand interactions, and MMGBSA revealed a low binding energy of -36.737 kcal/mol. Immune simulations indicated an effective immune response and peptide simulations demonstrated Globa D's stability in water, making it a potential candidate for pharmaceutical applications.

Conclusion: Globa D proved the best drug candidate against Neisseria gonorrhoeae by inhibiting PorB Porin protein chain A. Further in vitro and in vivo studies are recommended to validate these findings and explore clinical applications.

In this study, we leveraged a sophisticated active learning model to enhance virtual screening for SQLE inhibitors. The model's improved predictive accuracy identified compounds with significant advantages in binding affinity and thermodynamic stability. Detailed analyses, including molecular dynamics simulations and ADMET profiling, were conducted, particularly focusing on compounds CMNPD11566 and its derivative HCJ007. CMNPD11566 showed stable interactions with SQLE, while HCJ007 exhibited improved binding stability and more frequent interactions with key residues, indicating enhanced dynamic adaptability and overall binding effectiveness. ADMET data comparison highlighted HCJ007s superior profile in terms of lower toxicity and better drug-likeness. Our findings suggest HCJ007 as a promising candidate for SQLE inhibition, with significant improvements over CMNPD11566 in various pharmacokinetic and safety parameters. The study underscores the efficacy of computational models in drug discovery and the importance of comprehensive preclinical evaluations.

Active Pharmaceutical Ingredients-Ionic liquids (API-ILs) can increase drug solubility and bioavailability of solid drugs without changing the structure of drug molecules. In the present work, nonivamide (pelargonic acid vanillylamide, PAVA) was used as the active drug and choline (Ch) and citric acid (CA) were selected as the ions to prepare PAVA-based ionic liquid ([Ch][PAVA] and [PAVA]₃ [CA]), respectively. The characterization and physical properties of [Ch][PAVA] and [PAVA]₃ [CA], such as FT-IR spectra, 1H NMR spectra, thermal stability and hydrophilicity, were investigated. And the irritant effects of the PAVA-based ionic liquids were measured by the animal irritation experiment. [Ch][PAVA] has higher decomposition temperatures, better hydrophilicity and comparable irritant effects. The results show that the PAVA-based ILs synthesized in this study may potentially serve as a promising novel riot control agent.