Search Results (52)

We present a modular building block strategy for synthesizing phosphonated polyaromatic systems as an alternative to the conventional late-stage phosphonation of prefabricated aromatic scaffolds, which often requires harsh conditions and has limited tolerance for functional groups. A monophosphonated biphenyl building block was obtained via nickel-catalyzed phosphonation of dibromobiphenyl at 170 °C for three hours. This synthesis is more economical and milder than typical high-temperature palladium systems. In parallel, a borated pyrene derivative was prepared by Suzuki–Miyaura borylation. The final palladium-catalyzed Suzuki cross-coupling reaction produced the target compound, octaethyl(pyrene-tetrakis(biphenyl))tetrakis(phosphonate), Et₈-PyTPPE. Single-crystal X-ray diffraction reveals a centrosymmetric molecule that crystallizes in the triclinic space group P–1, with the inversion center located at the central C–C bond of the pyrene core. The pyrene unit is essentially planar, while the biphenylphosphonate arms are highly twisted relative to the core and to each other. The crystal packing is dominated by weak intermolecular interactions, and no significant π–π stacking is observed. Hirshfeld surface analysis shows that H···H (60.5%) and C···H (22.5%) contacts predominate, while O···H interactions (14.4%) with phosphoryl oxygen atoms represent the most relevant directed contacts. From photophysical investigations, Et₈-PyTPPE exhibits blue fluorescence (λ_em. = 452 nm) in solution and aggregation-induced red-shifted emission with nanosecond lifetimes in the solid state, confirming purely fluorescent behavior. Full article

Drought stress severely constrains plant growth and productivity. To mitigate water loss, plants primarily regulate stomatal aperture through the Abscisic acid (ABA) signaling pathway, where the Sucrose Nonfermenting 1-Related Protein Kinase 2 (SnRK2) family kinase Open Stomata 1 (OST1) acts as a central positive regulator. However, the upstream regulators that fine-tune OST1 activity remain incompletely characterized. Aliphatic Suberin Feruloyl Transferase (ASFT), a BAHD acyltransferase essential for suberin aromatic monomer biosynthesis, was previously uncharacterized regarding its function in leaves. Here, we report that ASFT negatively regulates drought tolerance in Arabidopsis thaliana by directly interacting with OST1 and inhibiting its autophosphorylation, thereby restricting stomatal aperture. Consistent with this, the asft mutant exhibited decreased water loss and enhanced survival under drought, whereas ASFT-overexpressing lines showed opposite phenotypes. BiFC, Co-IP and in vitro kinase assays confirmed that ASFT directly interacts with OST1 and suppresses its autophosphorylation, while dehydration-induced OST1 phosphorylation was elevated in the asft mutant. Genetic evidence confirmed that ASFT functions upstream of OST1. This study reveals a moonlighting role for this suberin biosynthetic enzyme in ABA signaling and provides a potential target for breeding drought-resistant crops. Full article

Steroidal compounds lie at the crossroads of inflammation and cancer, where modulation of common signaling pathways creates opportunities for dual-action therapeutic intervention. Accumulating evidence indicates that their anti-inflammatory and antitumor activities are frequently interconnected, reflecting shared molecular mechanisms that regulate immune signaling, oxidative stress, cell proliferation, and apoptosis. This review provides a critical and comparative analysis of major classes of bioactive steroids—including furanosteroids, neo-steroids, aromatic steroids, α,β-epoxy steroids, peroxy steroids, cyanosteroids, nitro- and epithio steroids, halogenated steroids (fluorinated, chlorinated, brominated, iodinated), and steroid phosphate esters—with emphasis on their dual anti-inflammatory and anticancer potential. More than one thousand steroidal metabolites derived from plants, fungi, marine organisms, bacteria, and synthetic sources are surveyed. While the majority exhibit either anti-inflammatory or antineoplastic activity alone, only a limited subset displays potent activity in both domains. Comparative evaluation highlights the structural features that favor dual functionality, including epoxide, peroxide, nitrile, nitro, halogen, and phosphate ester moieties, as well as rearranged or heteroatom-enriched steroidal frameworks. Where available, biological data from in vitro and in vivo assays (IC₅₀ values, enzyme inhibition, cytokine modulation, and antiproliferative effects) are summarized and critically compared. Special attention is given to rare natural metabolites—such as polyhalogenated marine steroids, phosphorylated sterols, and heteroatom-containing derivatives—as well as synthetic analogues designed to enhance cytotoxic or immunomodulatory efficacy. Mechanistically, steroids exhibiting dual activity commonly modulate convergent signaling pathways, including NF-κB, JAK/STAT, MAPK, PI3K/AKT, redox homeostasis, and apoptosis regulation. Collectively, these findings underscore the potential of structurally optimized steroids as multifunctional therapeutic agents and provide a framework for the rational design of next-generation anti-inflammatory and anticancer drugs. Full article

P-cresol, indole and indole-3-acetic acid (IAA) are catabolites of amino acids, formed by the gut microbiome. Most of these aromatic hydrocarbon derivatives are excreted by the colon before reentering the body to form “exogenous” protein-bound uremic toxins (PBUTs), which aggravate chronic kidney disease (CKD). Removal efficiencies of these PBUT precursors from model phosphate-buffered saline solutions by three different surface-modified nanoporous carbon adsorbents (PCs) were studied. PCs were produced by physicochemical and/or acid base activation of carbonized rice husk waste. Removal rates achieved values of 32–96% within a 3 h contact time. High micro/mesoporosity and surface chemistry of the N- and P-doped biochars were established by N₂ adsorption studies, SEM/EDS analysis, XPS and FT-IR-spectroscopy. The ammoxidized PC-N1 had the highest adsorption capacity (1.97 mmol/g for IAA, 2.43 mmol/g for p-cresol and 2.42 mmol/g for indole), followed by “urea-nitrified” PC-N2, whilst the phosphorylated PC-P demonstrated the lowest adsorption capacity for these solutes. These results do not correlate with the total pore volume values for PC-N2 (0.91 cm³/g) < PC-P (1.56 cm³/g) < PC-N1 (1.84 cm³/g), suggesting that other parameters such as the micropore volume (PC-N1 > PC-N2 > PC-P) and the interaction of surface chemical functional groups with the solutes play key roles in the adsorption mechanism. N-doped PC-N1 and PC-N2 have basic functional groups with higher affinity with acidic IAA and p-cresol. The ion-exchange mechanism of phenolic and indolic compound chemisorption by nanoporous carbon adsorbents, modified with surface N- and P-containing functional groups, has been proposed. Full article

Cinnamomum burmannii, renowned for its high essential oil content in leaves, is a pivotal species utilized for aromatic medicinal and industrial materials. This study focused on the functional identification of key regulatory enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXS) for terpenoid biosynthesis in the leaves of C. burmannii. A comprehensive approach, integrating terpenoid profiling assay and synthesis pathway construction, correlation analysis of terpenoid content and gene expression, and genome-wide analysis of DXS family across four developmental stages of leaves in three accessions of C. burmannii, led to the identification of CbDXS1 as a candidate regulatory gene for terpenoid biosynthesis. Overexpressing CbDXS1 in Arabidopsis enhanced plant growth, DXS enzyme activity, and chlorophyll content, and elevated transcriptional levels of terpenoid biosynthesis-related genes, leading to significant increases in terpenoid metabolites in transgenic leaves. Additionally, alterations in metabolite contents in the pathways of glycolysis, the tricarboxylic acid cycle, oxidative pentose phosphate, the Calvin cycle, oxidative phosphorylation, amino acid metabolism, and phytohormone biosynthesis suggested a potential redirection of carbon flux from primary metabolism to terpenoid biosynthesis and changes in endogenous phytohormone contents, the diterpene biosynthesis pathway, and amino acid metabolism, which may collectively contribute to terpenoid accumulation and phenotypic improvement in transgenic Arabidopsis. Our findings elucidated the multifaceted roles of CbDXS1 in modulating carbon flux and phytohormone biosynthesis for terpenoid production and plant development, offering potential strategies for engineering essential oil accumulation in the leaves of C. burmannii. Full article

In this research, we sought to methodically examine the protective effects of Gastrodia elata extract (GEE) on liver damage induced by D-galactose (D-gal) in mice and clarify the underlying mechanisms. The chemical composition of GEE was characterized using Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS), while network pharmacology analysis was employed to predict potential molecular targets and signaling pathways. A mouse model of liver injury was established through daily intraperitoneal injection of D-gal over a 42-day period, during which the hepatoprotective efficacy of GEE was evaluated. Biochemical, histopathological, and molecular analyses were subsequently performed. UPLC-MS/MS identified ingredients such as amino acids, aromatic compounds, fatty acids, and terpenoids in GEE. A network pharmacology analysis enabled the identification of 272 common targets linked to GEE and liver damage, demonstrating notable enrichment within the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. In vivo experiments demonstrated that GEE effectively alleviated D-gal-induced body weight loss and elevated liver index values, alleviated hepatic histological damage, and reduced serum levels of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Alkaline Phosphatase (ALP). Furthermore, GEE enhanced the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), decreased malondialdehyde (MDA) levels, and downregulated the mRNA expression of the pro-inflammatory cytokines Interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), and Tumor Necrosis Factor-alpha (TNF-α). Western blot analysis confirmed that GEE activated the PI3K/Akt pathway, as evidenced by increased ratios of phosphorylated Phosphatidylinositol 3-kinase/Phosphatidylinositol 3-kinase (p-PI3K/PI3K) and phosphorylated AKT/Protein Kinase B (p-AKT/AKT); restored the B-cell lymphoma 2-associated X protein/B-cell lymphoma-2 (Bax/Bcl-2) balance; and reduced cyclin-dependent kinase inhibitor 1 (p21) expression. The results suggest that GEE protects against D-gal-induced liver damage by reducing oxidative stress, inhibiting inflammatory responses, and modulating apoptosis through the activation of the PI3K/Akt signaling pathway, providing support for its potential use in hepatoprotection. Full article

This study focuses on the synthesis, properties, and comparative analysis of new flame-retardant compounds: coumarins and isophosphinolines. These compounds feature a diarylphosphine oxide (DAPO) substituent at the β-position relative to both the carbonyl and the phosphoryl groups. Various derivatives with halogens, phosphorus, and/or aromatics substituents were synthetized and their thermal stability and flammability were evaluated at the microscale by thermogravimetric analysis (TGA) and pyrolysis–combustion flow calorimetry (PCFC) in order to identify the most promising molecules for use as flame-retardant (FR) additives or comonomers. FTIR-coupled PCFC analysis was also carried out to study the combustion profiles of the molecules. Beyond the confirmation of some expected trends, such as the char promotion of phosphorus and flame inhibition of halogens, the study revealed some unexpected findings that warrant further investigation. These include the prominent role of the chlorine substitution position on the aromatic ring, as well as significant differences in FR performance between diastereoisomers. Full article

Nuclear factor-κB (NF-κB) signaling plays a pivotal role in regulating immune responses and is strongly implicated in cancer progression and inflammation-related diseases. The inhibitory κB kinases (IKKs), particularly IKKα, are central to modulating NF-κB activity, with distinct roles in the canonical and non-canonical signaling pathways. This study investigates the potential of selectively targeting IKKα to develop novel therapeutic strategies. A receptor–ligand interaction pharmacophore model was generated based on the co-crystallized structure of IKKα, incorporating six key features, two hydrogen bond acceptors, two hydrogen bond donors, one hydrophobic region, and one hydrophobic aromatic region. This model was used to virtually screen a diverse natural compound library of 5540 molecules, yielding 82 candidates that matched the essential pharmacophore features. Molecular docking and molecular dynamics simulations were subsequently employed to evaluate binding conformations, stability, and dynamic behavior of the top hits. The end-state free energy calculations (gmx_MMPBSA) further validated the interaction strength and stability of selected compounds. To experimentally confirm their inhibitory potential, key compounds were tested in LPS-stimulated RAW 264.7 cells, where they significantly reduced IκBα phosphorylation. These findings validate the integrative computational-experimental approach and identify promising natural compounds as selective IKKα inhibitors for further therapeutic development in cancer and inflammatory diseases. Full article

This review covers preclinical studies of stilbene derivative compounds (both natural and synthetic) with potential preventive and therapeutic effects against Alzheimer’s disease (AD). AD is a worldwide neurodegenerative disease characterized by the destruction of nerve cells in the brain and the loss of cognitive function due to aging. Stilbenes are a unique class of natural phenolic compounds distinguished by a C6-C2-C6 (1,2-diphenylethylene) structure and two aromatic rings connected by an ethylene bridge. Stilbenes’ distinct features make them an intriguing subject for pharmacological research and development. Several preclinical studies have suggested that stilbenes may have neuroprotective effects by reducing Aβ generation and oligomerization, enhancing Aβ clearance, and regulating tau neuropathology through the prevention of aberrant tau phosphorylation and aggregation, as well as scavenging reactive oxygen species. Synthetic stilbene derivatives also target multiple pathways involved in neuroprotection and have demonstrated promising biological activity in vitro. However, some properties of stilbenes, such as sensitivity to physiological conditions, low solubility, poor permeability, instability, and low bioavailability, limit their usefulness in clinical applications. To address this issue, current investigations have developed new drug delivery systems based on stilbene derivative molecules. This review aims to shed light on the development of next-generation treatment strategies by examining in detail the role of stilbenes in Alzheimer’s pathophysiology and their therapeutic potential. Full article

It was shown for the first time that diaryl(hetaryl)ketones are capable of directly phosphorylating with red phosphorus in the superbase suspension KOH/DMSO(H₂O) at 85 °C for 1.5 h to afford potassium bis(diaryl(hetaryl)methyl)phosphates that were earlier inaccessible in a yield of up to 45%. The ESR data demonstrate that unlike previously published phosphorylation with elemental phosphorus, this new phosphorylation reaction proceeds via a single electron transfer from polyphospide anions to diaryl(hetaryl)ketones. This is the first example of the C-O-P bond generation during the phosphorylation with elemental phosphorus in strongly basic media, which usually provides C-P bond formation. Full article

Phenolic compounds are an extensive group of natural and anthropogenic organic substances of the aromatic series containing one or more hydroxyl groups. The main sources of phenols entering the environment are waste from metallurgy and coke plants, enterprises of the leather, furniture, and pulp and paper industries, as well as wastewater from the production of phenol–formaldehyde resins, adhesives, plastics, and pesticides. Among this group of compounds, phenol is the most common environmental pollutant. One of the cheapest and most effective ways to combat phenol pollution is biological purification. However, the inability of bacteria to decompose high concentrations of phenol is a significant limitation. Due to the uncoupling of oxidative phosphorylation, phenol concentrations above 1 g/L are toxic and inhibit cell growth. This article presents data on the biodegradative potential of Rhodococcus opacus strain 3D. This strain is capable of decomposing a wide range of toxicants, including phenol. In the present study, cell growth with phenol, growth after rest, growth of immobilized cells before and after rest, phase contrast, and scanning microscopy of immobilized cells on fiber were studied in detail. The free-living and immobilized cells can decompose phenol concentrations up to 1.5 g/L and 2.5 g/L, respectively. The decomposition of the toxicant was catalyzed by the enzymes catechol 1,2-dioxygenase and cis,cis-muconate cycloisomerase. The role of protocatechuate 3,4-dioxygenase in biodegradative processes is discussed. In this work, it is shown that the immobilized cells can be stored for a long time (up to 2 years) without significant loss of their degradation activity. An assessment of the induction of genes potentially involved in this process was taken. Based on our investigation, we can conclude that this strain can be considered an effective destructor that is capable of degrading phenol at high concentrations, increases its biodegradative potential during immobilization, and retains this ability for a long storage time. Therefore, the strain can be used in biotechnology for the purification of aqueous samples at high concentrations from phenolic contamination. Full article

Obesity is a chronic disease that profoundly impacts human health, and the role of plant-based formulas (PBFs) in combating obesity has garnered significant interest. Studies have revealed that fermentation significantly enhances the taste, aroma, quality, and health benefits of PBF water extract, with pasteurization being the preferred sterilization technology. However, few studies have investigated the effects of pasteurization on the active components and potential functions of PBF water extract fermentation broth. To examine the impact of pasteurization on fermented water extract of Millettia speciosa Champ (FH08F) and its potential anti-obesity properties, the components of FH08F and thermal-pasteurized FH08F (FH08FS) were analyzed in this study. The analysis revealed a substantial rise in ester content following sterilization. This can be attributed to the acidic environment that promotes the esterification reaction during the heating phase. Network pharmacology was employed to thoroughly examine seven active components of upregulated compounds (URCs) with potential obesity targets, which constituted 92.97% of the total URC content, and four of them were nitrogen-containing aromatic heterocyclic compounds (NAHCs), which accounted for 90.33% of the total URC content. Upregulated NAHCs appear to actively contribute to efficacy against obesity. Molecular docking analyses have shown that theophylline, an NAHC, has the strongest binding affinity with the obesity-related target PTGS2 (Prostaglandin G/H synthase 2, 5FLG). These results imply that theophylline may directly activate PKA/PKG-mediated phosphorylated hormone-sensitive lipase (p-HSL), thereby promoting lipolysis through the cAMP signaling pathway and stimulating the catabolism of triglycerides (TGs) to combat obesity. In conclusion, pasteurization substantially alters the composition of FH08F, and NAHCs are likely to play a significant role in its potential anti-obesity function. These findings provide a scientific foundation for the potential therapeutic effect of FH08FS on obesity and associated metabolic diseases. Full article

Background/Objective: Maintaining intracellular adenosine triphosphate (ATP) levels is essential for numerous cellular functions, including energy metabolism, muscle contraction, and nerve impulse transmission. ATP is primarily synthesized in mitochondria through oxidative phosphorylation. It is also generated in the cytosol under anaerobic conditions using phosphocreatine (PCr) as a phosphate donor to adenosine diphosphate. However, the intracellular delivery of exogenous PCr is challenging as it does not readily cross the plasma membrane. This complicates the use of PCr as a therapeutic agent to maintain energy homeostasis or to treat conditions like cerebral creatine deficiency syndrome (CDS), which results from defective creatine transporters. Methods: This study employs the use of fusogenic liposomes to deliver PCr directly into the cytosol, bypassing membrane impermeability issues. We engineered various 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based fusogenic liposomes, incorporating phospholipids such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in combination with phospholipid-aromatic dye components to facilitate membrane fusion and to enhance the delivery of the PCr cargo. Liposomal formulations were co-loaded with membrane-impermeable chromophores and PCr and studied on live cells using confocal microscopy. Conclusions: We demonstrated the successful intracellular delivery of these agents and observed a 23% increase in intracellular ATP levels in cells treated with PCr-loaded liposomes. This increase was not observed with free PCr, confirming the effectiveness of the liposome-based delivery system. Additionally, cell viability assays showed minimal toxicity from the liposomes. Our results indicate that fusogenic liposomes are a promising method for the delivery of PCr (and potentially other cell-impermeable therapeutic agents) to the cellular cytosol. The approach demonstrated here could be advantageous for treating energy-related disorders and improving cellular energy homeostasis. Full article

Phosphorus is a key element for identifying past human activity. Recently, phosphorus analyses have been extended to archaeological objects, aiming at distinguishing how depositional contexts contribute to its enrichment. In archaeological pottery, phosphorus might depend on several manufacturing and postdepositional processes (i.e., addition of organic temper, pigments, diagenetic incorporation). We analyzed by XRD, XRF, and mid-infrared (FTIR-ATR) spectroscopy 178 pots from eight NW Spain archaeological sites. These sites encompass different chronologies, contexts, and local geology. The phosphorus content was highly variable (224–27,722 mg kg⁻¹) overall but also between archeological sites (1644 ± 487 to 13,635 ± 6623 mg kg⁻¹) and within archaeological sites (4–36, max/min ratio). No phosphate minerals were identified by XRD nor FTIR-ATR, but correlations between phosphorus content and MIR absorbances showed maxima at 1515 and 980 cm⁻¹, suggesting the presence of two sources: one organic (i.e., phosphorylated aromatic compounds) and another inorganic (i.e., albite and K-feldspar). Phosphorylated aromatics were most likely formed during pottery firing and were preserved due to their high resistance to temperature and oxidation. Meanwhile, albite and K-feldspar are among the P-bearing minerals with higher P concentrations. Our results suggest that P content is related to intentional and non-intentional actions taken in the pottery production process. Full article

The electrophilic activation of various substrates via double or even triple protonation in superacidic media enables reactions with extremely weak nucleophiles. Despite the significant progress in this area, the utility of organophosphorus compounds as superelectrophiles still remains limited. Additionally, the most common superacids require a special care due to their high toxicity, exceptional corrosiveness and moisture sensitivity. Herein, we report the first successful application of the “Brønsted acid assisted Brønsted acid” concept for the superelectrophilic activation of 2-hydroxybenzo[e][1,2]oxaphosphinine 2-oxides (phosphacoumarins). The pivotal role is attributed to the tendency of the phosphoryl moiety to form hydrogen-bonded complexes, which enables the formation of dicationic species and increases the electrophilicity of the phosphacoumarin. This unmasks the reactivity of phosphacoumarins towards non-activated aromatics, while requiring only relatively non-benign trifluoroacetic acid as the reaction medium. Full article