Search Results (79)

Staphylococcus aureus is a major cause of skin and soft tissue infections, necessitating the development of new topical agents with rapid bactericidal activity and low resistance potential. Here, we evaluated the antibacterial activity of a pyrazolone copper complex (P-FAH-Cu-phen) against S. aureus, investigated its in vitro mode of action, and its assessed therapeutic efficacy in a murine model of S. aureus-infected skin trauma. P-FAH-Cu-phen exhibited potent bactericidal activity (minimum inhibitory concentration [MIC] 1.4 μg/mL; minimum bactericidal concentration [MBC] 2.8 μg/mL) and rapid killing (>91% eradication within 2.5 min), with no detectable MIC increase under the tested serial passaging conditions. Cell-envelope dysfunction was evidenced by increased supernatant alkaline phosphatase activity, elevated leakage of nucleic acids and proteins, and reduced membrane-associated Na⁺/K⁺- and Ca²⁺/Mg²⁺-ATPase activities. At sub-inhibitory concentrations, P-FAH-Cu-phen reduced haemolytic and coagulase activities, modulated virulence gene expression (sea, hla, agrA), and inhibited biofilm formation and biofilm-associated metabolic activity. In vivo, topical treatment accelerated wound closure and histopathological repair, increased hydroxyproline content, reduced bacterial burden, and lowered TNF-α and IL-10 levels in wound tissues. Collectively, P-FAH-Cu-phen shows multi-faceted anti-infective activity and exhibits further development as a topical candidate for S. aureus-infected skin wounds. Full article

A new solvent extraction system for the removal of 4f ions (Ln³⁺) from water by use of chelating ligands (HLn, n = 5, 6, 7, and 8) composed of heterocyclic receptors and one β-dicarbonyl fragment is reported. The covalent attachment of a β-dicarbonyl unit to a saturated N-heterocycle with variable ring size resulted in a cooperative interaction within the receptor for Ln³⁺ transfer, which remarkably enhanced the efficiency of the process. The intramolecular cooperative effect was observed only in the ionic liquid (IL) solvent system, providing a several-fold increase in extraction performance for Ln³⁺ ions (La, Nd, Eu and Dy) over chloroform. Thus, it is not possible to confirm that an identical reaction mechanism operated in both liquid systems: IL or CHCl₃. The existence of neutral chelates of the type LnL₃ or anionic lanthanoid complexes [LnL₄⁻] in an ionic medium during the solvent extraction process applying various solvent systems has been established hitherto. Consequently, the Ln³⁺ ion was held by HLn molecules more rigidly in an IL medium ([C₁C_nim⁺]/[C₁C₄pyr⁺]/[C₁C₄pip⁺][Tf₂N⁻], n = 4, 6, 8, 10) than in chloroform, representing an important factor dominating the magnitude of the intramolecular cooperative effect of the chelating ligands for Ln³⁺ ions. The effect of the diluent’s chemical nature on the metal extraction and separation has been studied and discussed thoroughly. Furthermore, competitive solvent extraction and separation studies with various s-, p-, d-, and f-ions of the periodic table revealed that the magnitude of the intramolecular cooperative effect depends on the suitability between the metal ion size and the cavity size or flexibility of the HLn compounds. In addition, the solvent extraction process of 12 refractory metals and 8 platinum group metals with the synthesized chelating extractants is also investigated in different organic liquid media. Full article

Glycogen synthase kinase-3 beta (GSK-3β) is a multifunctional serine/threonine kinase mediating multiple cellular functions, such as differentiation, apoptosis, and cell proliferation. Because of their ability to alter carcinogenic pathways, GSK-3β inhibitors are being explored for the development of anticancer molecules. In the present study, we synthesized and evaluated the cytotoxic properties of a series of twenty indole–triazole-linked pyrazolone derivatives, 10Aa–Ed. All derivatives were characterized by FTIR, ¹H/¹³C NMR, and high-resolution mass spectrometry (HRMS) methods. All compounds and standards, sunitinib and 5-Fluorouracil (5-FU), were screened against four adherent cell lines, including pancreatic adenocarcinoma (Capan-1), colorectal carcinoma (HCT-116), glioblastoma(LN229), and lung carcinoma (NCI-4460), and four non-adherent cell lines, including acute myeloid leukemia (HL-60), chronic myeloid leukemia (K562), T lymphoblast (MOLT4), and non-Hodgkin lymphoma (Z138). Among the screened derivatives, molecule 10Aa showed cytotoxicity against MOLT 4, Z138, and HL60 with CC₅₀ values of 14.45 μM, 15.34 μM, and 17.56 μM, respectively. GSK-3β kinase inhibition was evaluated with the 10Aa, which is capable of inhibiting GSK-3β in a dose-dependent manner. Additionally, molecular docking was performed to estimate the correlation between invitro data and GSK-3β binding affinity. The outcomes of the invitro experiments demonstrated strong concordance with the insilico data. The discovery yielded compounds 10Aa and 10Cd, which can be modified to create effective anticancer agents that target GSK-3β. Full article

Background/Objectives: Epilepsy is characterized by unpredictable seizures and drug resistance, along with rising antimicrobial resistance (AMR), highlighting the urgent need for innovative dual-action therapies. This study aimed to design, develop, and evaluate novel pyrazolone derivatives for a dual antimicrobial and antiepileptic potential. Methods: Novel pyrazolone derivatives were designed, synthesized (using 2,4-dinitrophenylhydrazine/semicarbazide condensation with ethyl acetoacetate), and evaluated through molecular docking against antimicrobial (4URM, 3FYV, 3FRA) and neuronal targets (4COF, 5TP9, 5L1F). The in vitro antimicrobial activity was assessed against Gram-positive (S. aureus) and in vitro Gram-negative (E. coli, P. aeruginosa) strains via agar cup plate assays, while in vivo antiepileptic efficacy was tested in a PTZ-induced seizure model in Swiss albino mice. Results: Compound IIa showed potent dual activity, inhibiting E. coli (9 mm zone at 80 μg/mL) and S. aureus (9.5 mm at 80 μg/mL), alongside a significantly delayed seizure onset in the PTZ-induced mouse model (100% survival rate, 45 sec delayed seizure onset, p < 0.001). Compounds Ia and Id showed selective activity against E. coli (6 mm at 80 μg/mL) and P. aeruginosa (7 mm at 80 μg/mL), respectively. Docking studies revealed that compound IIa has a superior binding affinity (−7.57 kcal/mol for 3FYV) compared to standards, driven by hydrogen bonds (SER X: 49) and hydrophobic interactions (LEU X: 20). Conclusions: This study presents a novel approach by proposing a rationally designed pyrazolone scaffold exhibiting both antimicrobial and antiepileptic activity, which integrates in silico modeling with experimental validation. Compound IIa emerged with preliminary dual biological activities, exhibiting strong antibacterial activity, a superior binding affinity toward both bacterial and neuronal targets, and notable seizure prevention in vivo. These findings show the potential of multifunctional pyrazolone derivatives as a new treatment strategy for addressing drug-resistant infections linked to epilepsy and support further optimization toward clinical development. Full article

Background: In this research work, novel pyrazolone-derived oxadiazole-based benzamide derivatives (1–10) were synthesized through unique and facile synthetic routes. Introduction: These scaffolds were designed to be therapeutically more effective and have fewer side effects. Methods: To confirm the structure of analogs in detail, we employed ¹HNMR, ¹³CNMR, and HREI-MS spectroscopy. The potential of all derivatives was tested by screening them against alpha-amylase and alpha-glucosidase in comparison with reference anti-diabetic drug acarbose (4.50 ± 0.20 µM and 4.90 ± 0.30 µM). Results & Discussion: Among all tested analogs and standard drugs, derivative 3 proved to be the most promising candidate. It exhibited the most powerful inhibitory effect (IC₅₀ = 3.20 ± 0.20 µM and 3.60 ± 0.10 µM). To further investigate its activity, the experimental results were supported by in silico investigations. Molecular docking demonstrated strong and viable interactions between enzymes and the most potent compound. DFT calculations validated the electronic configuration, stability, and reactivity of lead molecules. Furthermore, the ADMET profile predicted the favorable drug likeness properties and low toxicity. The results of docking were further confirmed via molecular dynamics analysis, whereas the pharmacophore model of analog 3 supports the formation of a stable hydrogen bond network of derivatives with the receptor site of the enzyme. Conclusions: Collectively in silico and in vitro results underscore the therapeutic potential of these derivatives for the effective treatment of diabetes in the future. Full article

In this paper, a toxicological investigation was carried out on a series of azoic direct dyes generally with an affinity for cellulosic fibers, presenting symmetrical and asymmetrical structures having as a central component a non-carcinogenic, mutagenic, or teratogenic and accessible precursor potential substitute for benzidine, namely 4,4′-diaminobenzanilide, and, as coupling components, 2-hydroxybenzoic acid, 2-hydroxy-3,6-naphthalenesulfonic acid, 2-amino-8-hydroxynaphthalene-6-sulfonic acid, 1-amino-8-hydroxynaphthalene-3,6-disulfonic acid, 1-(4′-sulfophenyl)-3-methyl-5-pyrazolone, and 2-hydroxy-6-naphthalenesulfonic acid, respectively. For the purpose of their safe use, this study shows the results regarding the toxicity of the above-mentioned dyes, obtained through biological tests on colonies of Hydractinia echinata (H. echinata). The toxicity tests were performed on heterotrophic bacteria cultures obtained from the Bega River. The minimum toxic concentration was monitored using the dilutions 0.6 g/L, 24 g/L, and 48 g/L, obtained by dilution of a stock solution of 60 g/L. The symmetric dye with the coupling component 2-hydroxybenzoic acid presents the highest degree of toxicity, the lowest being shown by dyes with symmetric and asymmetric structures with the following coupling components: 2-amino-8-hydroxynaphthalene-6-sulfonic acid, 1-amino-8-hydroxynaphthalene-3,6-disulfonic acid, 1-(4′-sulfophenyl)-3-methyl-5-pyrazolone, and 2-hydroxy-6-naphthalenesulfonic acid. Full article

Artisanal and small-scale gold mining (ASGM) in Burkina Faso increasingly relies on cyanide, intensifying concerns about environmental contamination and human exposure. This study assessed free cyanide levels in water and soil across three ASGM sites—Zougnazagmiline, Guido, and Galgouli. Water samples (surface and groundwater) and topsoil (0–20 cm) were analyzed using the pyridine–pyrazolone method. Data were statistically and spatially processed using SPSS version 29.0 and the Google Earth Engine in conjunction with QGIS version 3.34, respectively. A site conceptual model (SCM) was also developed, based on the literature review, field observations, and validation by multidisciplinary experts in public health, toxicology, ecotoxicology, environmental engineering, and the mining sector, through a semi-structured survey. The results showed that 9.26% of the water samples exceeded the WHO guideline (0.07 mg/L), with peaks of 1.084 mg/L in Guido and 2.42 mg/L in Galgouli. At Zougnazagmiline, the water type differences were significant (F = 64.13; p < 0.001), unlike the other sites. In the soil, 29.36% of the samples exceeded 0.5 mg/kg, with concentrations reaching 9.79 mg/kg in Galgouli. A spatial analysis revealed pollution concentrated near the mining areas but spreading to residential and agricultural zones. The validated SCM integrates pollution sources, transport mechanisms, exposure routes, and vulnerable populations, offering a structured tool for environmental monitoring and health risk assessment in cyanide-impacted mining regions. Full article

A zinc complex bearing a pyrazolone-based azomethine ligand has been synthesized for blue-emitting organic light-emitting diodes (OLEDs). The azomethine ligand H₂L and the complex [ZnL·H₂O] were characterized by IR, 1H NMR, XRD, and TGA/DSC techniques. According to a single-crystal X-ray diffraction analysis, the complex [ZnL·H₂O] has a molecular structure. Its solid-state PL maxima appear to be at 416 nm and emit moderate blue emission with a quantum yield (QY) of 2%, with a dehydrated form of the complex showing greater efficiency with a QY of 55.5%. ZnL-based electroluminescent devices for OLED applications were fabricated. The devices exhibit blue emission with brightness up to 5300 Cd/A. Full article

Achieving superior circularly polarized luminescence brightness (B_CPL) is an important subject and continuous challenge for chiroptical materials. Herein, by applying a binary molecular design for the synthesis of chiral organo-Tb³⁺ molecules, a novel pair of mononuclear chiral tris-pyrazolate-Tb³⁺ enantiomers, [Tb(PMIP)₃(R,R-Ph-PyBox)] (2) and [Tb(PMIP)₃(S,S-Ph-PyBox)] (5), have been synthesized and characterized. The three 1-phenyl-3-methyl-4-(isobutyryl)-5-pyrazolone (HPMIP) ligands play the role of efficient luminescence sensitizers and strong light-harvesting antennas, while the enantiopure 2,6-bis(4-phenyl-2-oxazolin-2-yl) pyridine ligand (R,R/S,S-Ph-PyBox) is employed as the strong point-chiral inducer. With the proper combination of the HPMIP and Chiral-Ph-PyBox within the Tb³⁺ enantiomers, strong (PMIP)⁻-centered π-π^* electronic absorption (ε_{263 nm} = 38,400–39,500 M⁻¹ cm⁻¹) and brilliant high-purity ligand-sensitized Tb³⁺-centered green luminescence (Φ_PL = 47–48%) were observed. In addition, a clear circularly polarized luminescence (CPL) activity (|g_lum| = 0.096–0.103) was also observed, resulting in a strong B_CPL (610–623 M⁻¹ cm⁻¹) for the two Tb³⁺ enantiomers from the hypersensitive transitions. Our results offer an effective path to develop high-performance chiroptical organo-Tb³⁺ luminophores. Full article

Metamizole, or dipyrone, has been used for decades as a non-narcotic analgesic, providing pain relief from musculoskeletal disorders and antipyretic and antispasmolytic properties. Despite being in use since the 1920s, its mechanism of action still needs to be discovered. Despite causing fewer adverse effects when compared to other analgesics, its harmful effects on the blood and lack of evidence regarding its teratogenicity make the usage of the drug questionable, which has led to it being removed from the drug market of various countries. This narrative review aims to provide a detailed insight into the mechanism of action and efficacy, comparing its effectiveness and safety with other classes of drugs and the safety profile of metamizole. Full article

Catalyzed by Rh₂(esp)₂ (10 mol%) and (±)-BINAP (20 mol%) in DCE at 80 °C, the cascade assembly between diazobarbiturates and alkylidene pyrazolones proceeded readily and produced spiro-furopyrimidines in 38–96% chemical yields. The chemical structure of the prepared spirofuro-pyrimidines was firmly confirmed by X-ray diffraction analysis. Full article

The goal of this study was directed to synthesize a novel class of annulated compounds containing difuro[3,2-c:3′,2′-g]chromene. Friedländer condensation of o-aminoacetyl derivative 3 was performed with some active methylene ketones, namely, 1,3-cyclohexanediones, pyrazolones, 1,3-thiazolidinones and barbituric acids, furnished furochromenofuroquinolines (4,5), furochromenofuropyrazolopyridines (6–8), furochromenofurothiazolopyridines (9,10) and furochromenofuropyridopyrimidines (11, 12), respectively. Also, condensation of substrate 3 with 5-amine-3-methyl-1H-pyrazole and 6-amino-1,3-dimethyluracil, as cyclic enamines, resulted in polyfused systems 13 and 14, respectively. In vitro antimicrobial efficiency of the prepared heterocycles against microbial strains exhibited variable inhibition action, where compound 3 was the most effective against all kinds of microorganisms. A significant cytotoxic activity was seen upon the annulation of the starting compound with thiazolopyridine (9 and 10) as well as pyridopyrimidine moieties (11, 12 and 14). The spectroscopic and analytical results were used to infer the structures of the novel synthesized compounds. Full article

With the escalating demand for Astragalus polysaccharides products developed from Radix Astragali (RA), the necessity for quality control of polysaccharides in RA has become increasingly urgent. In this study, a specific method for the simultaneous determination of seven monosaccharides in polysaccharides extracted from Radix Astragali (RA) has been developed and validated using ultra-performance liquid chromatography equipped with an ultraviolet detector (UHPLC-UV) for the first time. The 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatizations were separated on a C18 column (Waters ACQUITY^TM, Milfor, MA, USA, 1.8 µm, 2.1 × 100 mm) using gradient elution with a binary system of 5 mm ammonium formate (0.1% formic acid)-acetonitrile for 24 min. Additionally, seven monosaccharides showed good linear relationships (R², 0.9971–0.9995), adequate precision (RSD < 4.21%), and high recoveries (RSD < 4.70%). The established method was used to analyze 109 batches of RA. Results showed that the Astragalus polysaccharides (APSs) mainly consist of mannose (Man), rhamnose (Rha), glucose (Glu), galactose (Gal), arabinose (Ara), xylose (Xyl); and fucose (Fuc); however, their composition was different among RA samples from different growth patterns, species, growth years, and origins, and the growth mode of RA and the age of wild-simulated RA can be accurately distinguished by principal component analysis (PCA). In addition, the immunological activity of APSs were also evaluated jointly by measurement of the NO release with RAW264.7, with the results showing that APSs have a promoting effect on the release of NO and exhibit a significant correlation with Man, Glu, Xyl, and Fuc contents. Accordingly, the new established monosaccharides analytical method and APS-immune activity determination in this study can provide a reference for quality evaluation and the establishment of quality standards for RA. Full article

In today’s evolving global world, the pharmaceutical sector faces an emerging challenge, which is the rapid surge of the global population and the consequent growth in drug production demands. Recognizing this, our study explores the urgent need to strengthen pharmaceutical production capacities, ensuring drugs are allocated and stored strategically to meet diverse regional and demographic needs. Summarizing our key findings, our research focuses on the promising area of drug demand forecasting using artificial intelligence (AI) and machine learning (ML) techniques to enhance predictions in the pharmaceutical field. Supplied with a rich dataset from Kaggle spanning 600,000 sales records from a singular pharmacy, our study embarks on a thorough exploration of univariate time series analysis. Here, we pair conventional analytical tools such as ARIMA with advanced methodologies like LSTM neural networks, all with a singular vision: refining the precision of our sales. Venturing deeper, our data underwent categorisation and were segmented into eight clusters premised on the ATC Anatomical Therapeutic Chemical (ATC) Classification System framework. This segmentation unravels the evident influence of seasonality on drug sales. The analysis not only highlights the effectiveness of machine learning models but also illuminates the remarkable success of XGBoost. This algorithm outperformed traditional models, achieving the lowest MAPE values: 17.89% for M01AB (anti-inflammatory and antirheumatic products, non-steroids, acetic acid derivatives, and related substances), 16.92% for M01AE (anti-inflammatory and antirheumatic products, non-steroids, and propionic acid derivatives), 17.98% for N02BA (analgesics, antipyretics, and anilides), and 16.05% for N02BE (analgesics, antipyretics, pyrazolones, and anilides). XGBoost further demonstrated exceptional precision with the lowest MSE scores: 28.8 for M01AB, 1518.56 for N02BE, and 350.84 for N05C (hypnotics and sedatives). Additionally, the Seasonal Naïve model recorded an MSE of 49.19 for M01AE, while the Single Exponential Smoothing model showed an MSE of 7.19 for N05B. These findings underscore the strengths derived from employing a diverse range of approaches within the forecasting series. In summary, our research accentuates the significance of leveraging machine learning techniques to derive valuable insights for pharmaceutical companies. By applying the power of these methods, companies can optimize their production, storage, distribution, and marketing practices. Full article

Developing colorimetric devices for detecting chemical species is essential in many fields; nevertheless, developing effective chemosensors for many heavy and transition metal ions remains an important issue. As a result, in recent years, the use of colorimetric sensors for the selective and sensitive detection of metal ions has grown in popularity. Pyrazolones and their derivatives are heterocyclic compounds that have attracted interest due to their biological and pharmacological features. As a result, they have been used in various areas, including agriculture, medicine, organic synthesis, and analytical chemistry. However, the potential for chemosensing has yet to receive much attention. In this study, thiomethyl-substituted (4Z)-4-[(pyrazol-4-yl)methylene]pyrazolone was synthesized, and its ability to act as an optical chemosensor for several metals was evaluated. According to preliminary results, this molecule could be an optical chemosensor to detect Fe³⁺, Sn²⁺, and Al³⁺. Full article