Search Results (114)

In order to explore the essence of the anticoccidiosis of anticoccidial drugs under bioelectric currents, the intermolecular double-proton transfer and conformational transformation of 4-pyridone-3-carboxylic acid were investigated by quantum chemistry calculations (at the M06-2X/6-311++G**, M06-2X/aug-cc-pVTZ and CCSD(T)/aug-cc-pVTZ levels) and finite temperature string (FTS) under external electric fields. The solvent effect of H₂O on the double-proton transfer was evaluated by the integral equation formalism polarized continuum model. The results indicate that the influences of the external electric fields along the direction of the dipole moment on double-proton transfer are significant. The corresponding products are controlled by the direction of the external electric field. Due to the first-order Stark effect, some good linear relationships form between the changes of the structures, atoms in molecules (AIMs) results, surface electrostatic potentials, barriers of the transition state, and the external electric field strengths. From the gas to solvent phase, the barrier heights increased. The spatial order parameters (ϕ, ψ) of the conformational transformation could be quickly converged through the umbrella sampling and parameter averaging, and thus the free-energy landscape for the conformational transformation was obtained. Under the external electric field, there is competition between the double-proton transfer and conformational transformation. The external electric field greatly affects the cooperativity transfer, while it has little effect on the conformational transformation. This study is helpful in the selection and updating of anticoccidial drugs. Full article

Multicomponent reactions (MCRs) enable the efficient assembly of complex small molecules via multiple bond-forming events in a single step. However, individual MCRs typically yield products with similar core structures, limiting access to larger, more intricate scaffolds. Strategic selection of reactants allows the combination of distinct MCRs, thus facilitating the synthesis of advanced molecular architectures with potential biological significance. Using our previously reported method for performing the aza-Friedel Crafts multicomponent reaction under green heterogeneous conditions, we have incorporated some of the obtained products into diverse multicomponent reactions to generate, in an unprecedent approach, eight novel products, some of which were also characterized by two-dimensional NMR techniques. The biological properties of such products are under investigation. Full article

In this study, we synthesized and characterized new imidazole ligands containing pyridone groups, as well as mononuclear and binuclear ruthenium complexes, which are a new class of water-soluble metallacycles. We studied the antiproliferative activity of these compounds in vitro using the MTT assay on a panel of human cancer cell lines and on primary rat fibroblasts, where we observed a complete absence of cytotoxicity up to a concentration of 1000 µM. For the binuclear metallocycle compounds, we investigated their solubility in water, resistance to hydrolysis, and ability to induce apoptosis in tumor cells. Full article

Recently published data indicate that elevated circulating concentrations of N1-methyl-2-pyridone-5-carboxamide (2PY, also described as Met2PY) and N1-methyl-4-pyridone-5-carboxamide (4PY, also described as Met4PY), terminal catabolites of nicotinamide adenine dinucleotide (NAD⁺), are associated with cardiovascular disease (CVD) risk in humans. Previously, we and the others have shown that patients with advanced stages of chronic kidney disease (CKD) exhibit several-fold higher circulating 2PY and 4PY concentrations compared to healthy subjects or patients in the early stages of the disease. It is also well documented that patients with advanced CKD stages exhibit markedly elevated CVD risk, which is the main cause of premature death (in these patients). Therefore, we hypothesize that high concentrations of circulating 2PY and 4PY are important factors that may contribute to cardiovascular events and, ultimately, premature death in CKD patients. However, further, accurately controlled clinical research is needed to provide definitive answers concerning the role of 2PY and 4PY in CVD risk in CKD patients. Moreover, we are dealing with some issues related to the use of NAD⁺ precursors (NAD⁺ boosters) as drugs (also in CKD patients) and/or supplements. Due to the increase in circulating 2PY and 4PY levels during treatment with NAD⁺ boosters, these precursors should be used with caution, especially in patients with increased CVD risk. Full article

Simplified analogs of cortistatin A were synthesized and biologically evaluated to develop novel antitumor substances that target angiogenesis. To analyze the effect of substituents at positions corresponding to C-2 and/or C-4 of the A-ring, various pyrone- or pyridone-embedded analogs were designed and synthesized. Among the prepared analogs, the pyridone analog 19 bearing a methyl group at C-2 and a hydroxyl group at C-4 showed potent and selective growth inhibitory activity against human umbilical vein endothelial cells (HUVECs, IC₅₀ = 0.001 µM, selective index over that against human epidermoid carcinoma KB3-1 cells = 6400), exceeding those of natural products. The analog 19 of oral administration exhibited excellent in vivo antitumor activity in mice subcutaneously inoculated with sarcoma S180 cells. Full article

In this research, we successfully synthesized nitrogen-enriched microporous carbon through a meticulous process involving two different activation procedures. Initially, polybenzoxazine was carbonized at 800 °C to create a precursor material, which was then activated with two different activating agents (KOH and KMnO₄) at the same temperature. This activation significantly enhanced the material’s porosity, increasing its specific surface area from 335 m²/g (KOH activated) to 943 m²/g (KMnO₄ activated). XPS analysis confirmed the presence of nitrogen functionalities, including secondary-N, oxide-N, pyridone-N, and pyridine-N, which are critical for CO₂ adsorption. Adsorption tests demonstrated a high CO₂ uptake of 3.8 mmol/g at 25 °C and 1 bar, driven by a combination of physisorption (physical interaction with the surface area) and chemisorption (chemical interaction with nitrogen sites). This high adsorption capacity can be attributed to the carbon’s substantial surface area, significant micropore volume, and the interconnected network of pores, which together provide structural stability and facilitate the diffusion of CO₂ molecules. These findings suggest that this nitrogen-enriched microporous carbon, derived from polybenzoxazine, holds significant promise as a highly efficient material for applications in CO₂ capture and storage. Full article

4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) is a nicotinamide derivative, considered a new oncometabolite. 4PYR formation induced a cytotoxic effect on the endothelium. Elevated blood 4PYR concentration was observed in patients with cancer. Still, little is known about the metabolic and functional effects of 4PYR in this pathology. The study aimed to investigate whether this toxic accumulation of 4PYR may affect the activity of anticancer therapy with cyclophosphamide in the orthotropic model of breast cancer. Female Balb/c mice were injected with 4T1 breast cancer cells and assigned into three groups: treated with PBS (Control), cyclophosphamide-treated (+CP), 4PYR-treated (+4PYR), and mice treated with both 4PYR and CP(+4PYR+CP) for 28 days. Afterward, blood and serum samples, liver, muscle, spleen, heart, lungs, aortas, and tumor tissue were collected for analysis of concentrations of nucleotides, nicotinamide metabolites, and 4PYR with its metabolites, as well as the liver level of cytochrome P450 enzymes. 4PYR treatment caused elevation of blood 4PYR, its monophosphate and a nicotinamide adenine dinucleotide (NAD+) analog—4PYRAD. Blood 4PYRAD concentration in the +4PYR+CP was reduced in comparison to +4PYR. Tumor growth and final tumor mass were significantly decreased in +CP and did not differ in +4PYR in comparison to Control. However, we observed a substantial increase in these parameters in +4PYR+CP as compared to +CP. The extracellular adenosine deamination rate was measured to assess vascular inflammation, and it was higher in +4PYR than the Control. Treatment with 4PYR and CP caused the highest vascular ATP hydrolysis and adenosine deamination rate. 4PYR administration caused significant elevation of CYP2C9 and reduction in CYP3A4 liver concentrations in both +4PYR and +4PYR+CP as compared to Control and +CP. In additional experiments, we compared healthy mice without cancer, treated with 4PYR (4PYR w/o cancer) and PBS (Control w/o cancer), where 4PYR treatment caused an increase in the serum proinflammatory cytokine expression as compared to Control w/o cancer. 4PYR accumulation in the blood interferes with cyclophosphamide anticancer activity and induces a pro-inflammatory shift of endothelial extracellular enzymes, probably by affecting its metabolism by cytochrome P450 enzymes. This observation may have crucial implications for the activity of various anticancer drugs metabolized by cytochrome P450. Full article

Selenium compounds have garnered significant attention in the field of medicinal chemistry due to their unique biochemical properties and potential therapeutic applications for different pathologies. In this study, we report the synthesis of a new selenylated bis-pyridone compound using SeO₂ as the source of selenium. Detailed ¹H and ¹³C NMR characterizations and mass spectral analysis are given. Full article

The herbicide fluridone (1-methyl-3-phenyl-5-[3-trifluoromethyl (phenyl)]-4(1H)-pyridone) interferes with carotenoid biosynthesis in plants by inhibiting the conversion of phytoene to phytofluene. Fluridone also indirectly inhibits the biosynthesis of abscisic acid and strigolactones, and therefore, our study indirectly addresses the effect of reduced ABA on the roots and leaf buds development in stem cuttings of Salix babylonica L. ‘Tortuosa’. The stem cuttings were kept in distilled water (control) or in a solution of fluridone (10 mg/L) in natural greenhouse light and temperature conditions. During the experiments, morphological observations were carried out on developing roots and leaf buds, as well as their appearance and growth. After three weeks of continuous treatments, adventitious roots and leaf buds were collected and analysed. Identification and analysis of anthocyanins were carried out using micro-HPLC-MS/MS-TOF, while HPLC-MS/MS was used to analyse phenolic acids, flavonoids and salicinoids. The fluridone applied significantly inhibited root growth, but the number or density of roots was higher compared to the control. Contents of salicortin and salicin were several dozen times higher in leaf buds than in roots of willow. Fluridone increased the content of salicortin in roots and leaf buds and declined the level of salicin in buds. Fluridone also declined the content of most anthocyanins in roots but enhanced their content in buds, especially cyanidin glucoside, cyanidin galactoside and cyanidin rutinoside. Besides, fluridone markedly decreased the level of chlorophylls and carotenoids in the leaf buds. The results indicate that applied fluridone solution reduced root growth, caused bleaching of leaf buds, and markedly affected the content of secondary metabolites in the adventitious roots and leaf buds of S. babylonica stem cuttings. The paper presents and discusses in detail the significance of fluridone’s effects on physiological processes and secondary metabolism. Full article

In this work, we present new methods of synthesis of different molecules including a 2-pyridone nucleus. First, we prepared a series of 1H-free 2-pyridones and N-alkyl 2-pyridones from ethyl cyanoacetate, aromatic aldehydes, various acetophenone derivatives and ammonium acetate or diamino-alkane. These molecules have served as building blocks that, in conjunction with acyl chloride derivatives, glycoside derivatives, etc. have resulted in various heterocyclic hybrid structures carrying a 2-pyridone ring. Moreover, based on the cyano group reactivity of the 2-pyridone ring, we synthesized 5-pyridone 1H-tetrazole in a single step by a cycloaddition reaction [3 + 2] between 3-cyano-2-pyridone nitriles and sodium azide in the presence of metal-free L-proline. Full article

A method for the synthesis of C4-benzhydryl-functionalized 3,4-dihydropyridin-2-ones using complementary addition of benzhydryllithium and/or benzhydrylmagnesiate reagents to 2-pyridones, with high regioselectivity triggered by substituents, is described. A partially stereoselective cyclization was successfully demonstrated using TfOH and/or TIPSOTf as Brønsted and Lewis acids, respectively, leading to C6-phenyl-functionalized 7,8-benzomorphanones. It is also shown that the use of functionalized δ-enelactams obtained with an active methoxy-substituted benzyl group at C3 enabled the preparation of a new C3–C6 bridged system within the δ-lactam framework. Full article

Two new yellow azo pyridone derivatives, (E)-6-hydroxy-1-(3-methoxypropyl)-4-methyl-2-oxo-5-(p-tolyldiazenyl)-1,2-dihydropyridine-3-carbonitrile (APY-M) and 5,5′-((1E,1′E)-(methylenebis(4,1-phenylene))bis(diazene-2,1-diyl))bis(6-hydroxy-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile) (APY-D), were designed and synthesized as yellow colorants for image sensors. The properties of these new compounds were evaluated in both solution and color filter film forms, focusing on their optical and thermal characteristics. The molar extinction coefficient values of APY-M and APY-D in solution were found to be 2.7 × 10⁵ and 3.0 × 10⁵ L/mol·cm, respectively. The transmittance of the newly synthesized compounds met commercial requirements, showing values below 0.21% at 435 nm and above 97.1% at 530 nm. APY-D exhibited a molar extinction coefficient value in solution that was 1.15 times higher than that of the commercially used yellow colorant Disperse Yellow 241. Both newly synthesized compounds satisfied the decomposition temperature requirement of over 230 °C, which is essential for the color filter manufacturing process in image sensors. In particular, APY-D, with its dimeric structure and increased molecular weight, demonstrated enhanced thermal stability, with a 50 °C increase in decomposition temperature compared to Disperse Yellow 241. Color filter films for image sensors were fabricated using the new compounds, and their thermal resistance was evaluated. APY-D maintained its transmittance due to the enhanced thermal stability provided by its dimer structure and increased molecular weight. Consequently, APY-D is anticipated to be a promising candidate for use as a yellow colorant in image sensors, owing to its excellent optical and thermal properties. Full article

A novel methodology for the synthesis of 2-pyridones bearing a 2-pyridyl group on nitrogen and carbon atoms, starting from 2-bromopyridines, was developed employing a simple Ru(II)–KOPiv–Na₂CO₃ catalytic system. Unsubstituted 2-bromopyridine was successfully converted to the penta-heteroarylated 2-pyridone product using this method. Preliminary mechanistic studies revealed a possible synthetic pathway leading to the multi-heteroarylated 2-pyridone products, involving consecutive oxygen incorporation, a Buchwald–Hartwig-type reaction, and C–H bond activation. Full article

The Caf1/CNOT7 nuclease is a catalytic component of the Ccr4-Not deadenylase complex, which is a key regulator of post-transcriptional gene regulation. In addition to providing catalytic activity, Caf1/CNOT7 and its paralogue Caf1/CNOT8 also contribute a structural function by mediating interactions between the large, non-catalytic subunit CNOT1, which forms the backbone of the Ccr4-Not complex and the second nuclease subunit Ccr4 (CNOT6/CNOT6L). To facilitate investigations into the role of Caf1/CNOT7 in gene regulation, we aimed to discover and develop non-nucleoside inhibitors of the enzyme. Here, we disclose that the tri-substituted 2-pyridone compound 5-(5-bromo-2-hydroxy-benzoyl)-1-(4-chloro-2-methoxy-5-methyl-phenyl)-2-oxo-pyridine-3-carbonitrile is an inhibitor of the Caf1/CNOT7 nuclease. Using a fluorescence-based nuclease assay, the activity of 16 structural analogues was determined, which predominantly explored substituents on the 1-phenyl group. While no compound with higher potency was identified among this set of structural analogues, the lowest potency was observed with the analogue lacking substituents on the 1-phenyl group. This indicates that substituents on the 1-phenyl group contribute significantly to binding. To identify possible binding modes of the inhibitors, molecular docking was carried out. This analysis suggested that the binding modes of the five most potent inhibitors may display similar conformations upon binding active site residues. Possible interactions include π-π interactions with His225, hydrogen bonding with the backbone of Phe43 and Van der Waals interactions with His225, Leu209, Leu112 and Leu115. Full article

Cancer continues to be a major global health issue, ranking among the top causes of death worldwide. To develop novel antitumor agents, this study focused on the synthesis of a series of 21 novel furanopyridinone derivatives through structural modifications and functional enhancements. The in vitro anti-tumor activities of these compounds were investigated through the cytotoxicity against KYSE70 and KYSE150 and led to the identification of compound 4c as the most potent compound. At a concentration of 20 µg/mL, compound 4c demonstrated a remarkable 99% inhibition of KYSE70 and KYSE150 cell growth after 48 h. IC₅₀ was 0.655 µg/mL after 24 h. Additionally, potential anti-tumor cellular mechanisms were explored through molecular docking, which was used to predict the binding mode of 4c with METAP2 and EGFR, suggesting that the C=O part of the pyridone moiety likely played a crucial role in binding. This study provided valuable insights and guidance for the development of novel anticancer drugs with novel structural scaffolds. Full article