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1.
Anal Chim Acta ; 1316: 342861, 2024 Aug 08.
Article de Anglais | MEDLINE | ID: mdl-38969410

RÉSUMÉ

BACKGROUND: The high toxicity of hexavalent chromium [Cr (VI)] could not only cause harmful effects on humans, including carcinogenicity, respiratory issues, genetic damage, and skin irritation, but also contaminate drinking water sources, aquatic ecosystems, and soil, impairing the reproductive capacity, growth, and survival of organisms. Due to these harmful effects, detecting toxic Cr (VI) is of great significance. However, the rapid, simple, and efficient detection at a low Cr (VI) concentration is extremely challenging, especially in an acidic condition (existing as HCrO4-) due to its low adsorption free energy. RESULTS: A diketopyrrolopyrrole-based small molecule (DPPT-PhSMe) is designed and characterized to act as a chemosensor, which allows a high selectivity to Cr (VI) at an acidic condition with a low limit of detection to 10-8 M that is two orders of magnitude lower than the cut of limit (1 µM) recommended by World Health Organization (WHO). Mechanism study indicates that the rich sulfur atoms enhance the affinity to HCrO4-. Combining with favorable features of diketopyrrolopyrrole, DPPT-PhSMe not only allows dual-mode detection (colorimetric and spectroscopic) to Cr (VI), but also enables disposable paper-based sensor for naked-eye detection to Cr (VI) from fully aqueous media. The investigation of DPPT-PhSMe chemosensor for the quantification of Cr (VI) in real life samples demonstrates a high reliability and accuracy with an average percentage recovery of 102.1 % ± 4 (n = 3). SIGNIFICANCE: DPPT-PhSMe represents the first diketopyrrolopyrrole-derived chemosensor for efficient detection to toxic Cr (VI), not only providing a targeted solution to the bottleneck of Cr (VI) detection in acidic conditions (existing as HCrO4-) caused by its low adsorption free energy, but also opening a new scenario for simple, selective, and efficient Cr (VI) detection with conjugated dye molecules.


Sujet(s)
Chrome , Limite de détection , Pyrroles , Polluants chimiques de l'eau , Chrome/analyse , Pyrroles/composition chimique , Polluants chimiques de l'eau/analyse , Cétones/composition chimique , Cétones/analyse , Eau/composition chimique
2.
ACS Appl Mater Interfaces ; 16(24): 30611-30621, 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38857116

RÉSUMÉ

Polypyrrole (Ppy) is a biologically compatible polymer that is used as a matrix, in which drugs and enzymes can be incorporated by doping. Here, we suggest an inventive application of Ppy as a biorecognition film encapsulated with an antibody (Ab) as an alternative strategy for the on-site multistep functionalization of thiol-based self-assembled monolayers. The fabrication steps of the recognition films were followed by dropping pyrrole and Ab mixed solutions onto the electrode and obtaining a thin film by direct current electropolymerization. The efficiency of Ab immobilization was studied by using fluorescence microscopy and electrochemical (EC) methods. Finally, the Ab density was increased and immobilized in 1 min, and the sensing performance as an EC immunosensor was demonstrated using α-fetoprotein with a limit of detection of 3.13 pg/mL and sensing range from 1 pg/mL to 100 ng/mL. This study demonstrates the potential for electrochemical functionalization of biomolecules with high affinity and rapidity.


Sujet(s)
Anticorps immobilisés , Techniques électrochimiques , Polymères , Pyrroles , Pyrroles/composition chimique , Dosage immunologique/méthodes , Polymères/composition chimique , Techniques électrochimiques/méthodes , Anticorps immobilisés/immunologie , Anticorps immobilisés/composition chimique , Techniques de biocapteur/méthodes , Polymérisation , Alphafoetoprotéines/analyse , Alphafoetoprotéines/immunologie , Électrodes , Limite de détection , Humains
3.
J Hazard Mater ; 475: 134580, 2024 Aug 15.
Article de Anglais | MEDLINE | ID: mdl-38865829

RÉSUMÉ

In this research, a new material, chitosan/polypyrrole (CS/PPy), was synthesized and linked with the Cr(VI)-reducing bacterial strain YL3 to treat Cr(VI)-polluted soil. The findings demonstrated that the synergistic application of strain YL3 and CS/PPy achieved the greatest reduction (99.6 %). During the remediation process, CS/PPy served as a mass-storage and sustained release agent in the soil, which initially decreased the toxic effects of high concentrations of Cr(VI) on strain YL3, thereby enhancing the Cr(VI) reduction efficiency of strain YL3. These combined effects significantly mitigated Cr(VI) stress in the soil and restored enzyme activities. Furthermore, wheat growth in the treated soil also significantly improved. High-throughput sequencing of the microorganisms in the treated soil revealed that CS/PPy was not only effective at removing Cr(VI) but also at preserving the original microbial diversity of the soil. This suggests that the combined treatment using strain YL3 and CS/PPy could rehabilitate Cr(VI)-contaminated soil, positioning CS/PPy as a promising composite material for future bioremediation efforts in Cr(VI)-contaminated soils.


Sujet(s)
Dépollution biologique de l'environnement , Chitosane , Chrome , Microbacterium , Polymères , Pyrroles , Microbiologie du sol , Polluants du sol , Polluants du sol/métabolisme , Chrome/métabolisme , Chrome/composition chimique , Chitosane/composition chimique , Polymères/composition chimique , Polymères/métabolisme , Pyrroles/métabolisme , Pyrroles/composition chimique , Microbacterium/métabolisme , Triticum/métabolisme
4.
Environ Sci Pollut Res Int ; 31(30): 42521-42546, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38878243

RÉSUMÉ

The use of photocatalysis technology, specifically visible light photocatalysis that relies on sustainable solar energy, is the most promising for the degradation of contaminants. The interaction of conducting polymer and titanium dioxide (TiO2) leads to the exchange that enhances the alteration of the semiconductor's surface and subsequently decreases the bandgap energy. Polypyrrole (PPy) and TiO2 nanocomposites have promising potential for photocatalytic degradation. Chemically and electrochemical polymerization are two predominant methods for adding inorganic nanoparticles to a conducting polymer host matrix. The most commonly utilized method for producing PPy/TiO2 nanocomposites is the in-situ chemical oxidative polymerization technique. Immobilizing PPy/TiO2 on substrates causes more charge carriers (electron/hole pairs) to be produced on the surface of TiO2 and enhances the rate of photocatalytic degradation compared to pure TiO2. The increased surface charge affects how electron/hole pairs are formed when visible light is used. This study provides a comprehensive investigation into the synthesis, characterization, application, efficiency, and mechanism of PPy/TiO2 nanocomposites in the photocatalytic degradation process of various pollutants. Furthermore, the effect of stabilizing the TiO2/PPy nanocomposite on various substrates will be investigated. In conclusion, the review outlines the ongoing challenges in utilizing these photocatalysts and highlights the essential concerns that require attention in future research. Its objective is to help researchers better understand photocatalysts and encourage their use in wastewater treatment.


Sujet(s)
Nanocomposites , Polymères , Titane , Titane/composition chimique , Nanocomposites/composition chimique , Catalyse , Polymères/composition chimique , Pyrroles/composition chimique
5.
Int J Biol Macromol ; 273(Pt 1): 132962, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38848827

RÉSUMÉ

The preparation of natural polymer-based highly conductive hydrogels with reliable durability for applications in supercapacitors (SCs) is still challenging. Herein, a facile method to prepare alkaline lignin (AL)-based polypyrrole (PPy)-rich, high-conductive PPy@AL/PEGDGE gel was reported, where AL was used as a dopant, polyethylene glycol diglycidyl ether (PEGDGE) as a cross-linking agent, and PPy as a conducting polymer. The PPy@AL/PEGDGE gel electrode materials with hollow structures were prepared by electrochemical deposition and chemical etching method and then assembled into sandwich-shaped SCs. Cyclic voltammetry (CV), galvanotactic charge discharge (GCD), electrochemical impedance spectroscopy (EIS) and cycling stability tests of the PPy@AL/PEGDGE SCs were performed. The results demonstrated that the SCs can achieve a conductivity of 25.9 S·m-1 and a specific capacitance of 175 F·g-1, which was 127.4 % higher compared to pure PPy (77 F·g-1) electrode. The highest energy density and power density for the SCs were obtained at 23.06 Wh·kg-1 and 5376 W·kg-1, respectively. In addition, the cycling performance was also higher than that of pure PPy assembled SCs (50 %), and the capacitance retention rate can reach 72.3 % after 1000 cycles. The electrode materials are expected to be used as sensor and SCs devices.


Sujet(s)
Capacité électrique , Électrodes , Hydrogels , Lignine , Polymères , Pyrroles , Pyrroles/composition chimique , Lignine/composition chimique , Polymères/composition chimique , Hydrogels/composition chimique , Conductivité électrique , Techniques électrochimiques/méthodes
6.
Int J Biol Macromol ; 273(Pt 1): 132963, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38852725

RÉSUMÉ

Human chorionic gonadotropin (HCG), a vital protein for pregnancy determination and a marker for trophoblastic diseases, finds application in monitoring early pregnancy and ectopic pregnancy. This study presents an innovative approach employing electrochemical immunosensors for enhanced HCG detection, utilizing Anti-HCG antibodies and gold nanoparticles (AuNPs) in the sensor platform. Two sensor configurations were optimized: BSA/Anti-HCG/c-AuNPs/MEL/e-AuNPs/SPCE with [Fe(CN)6]3-/4- as a redox probe (1) and BSA/Anti-HCG/PPy/e-AuNPs/SPCE using polypyrrole (PPy) as a redox probe (2). The first sensor offers linear correlation in the 0.10-500.00 pg∙mL-1 HCG range, with a limit of detection (LOD) of 0.06 pg∙mL-1, sensitivity of 32.25 µA∙pg-1∙mL∙cm-2, RSD <2.47 %, and a recovery rate of 101.03-104.81 %. The second sensor widens the HCG detection range (40.00 fg∙mL-1-5.00 pg∙mL-1) with a LOD of 16.53 fg∙mL-1, ensuring precision (RSD <1.04 %) and a recovery range of 94.61-106.07 % in serum samples. These electrochemical immunosensors have transformative potential in biomarker detection, offering enhanced sensitivity, selectivity, and stability for advanced healthcare diagnostics.


Sujet(s)
Techniques de biocapteur , Gonadotrophine chorionique , Techniques électrochimiques , Or , Limite de détection , Nanoparticules métalliques , Polymères , Pyrroles , Gonadotrophine chorionique/sang , Gonadotrophine chorionique/analyse , Gonadotrophine chorionique/immunologie , Or/composition chimique , Humains , Nanoparticules métalliques/composition chimique , Techniques électrochimiques/méthodes , Techniques de biocapteur/méthodes , Polymères/composition chimique , Pyrroles/composition chimique , Dosage immunologique/méthodes , Dosage immunologique/instrumentation , Hexacyanoferrates III/composition chimique , Femelle
7.
Chem Pharm Bull (Tokyo) ; 72(5): 518-523, 2024.
Article de Anglais | MEDLINE | ID: mdl-38825446

RÉSUMÉ

We have developed a series of 2-monoaryl-5-diarylmethylene analogs of the green fluorescent protein chromophore to study their viscosity-induced emission (VIE) properties. The analogs were synthesized by a condensation with methyl imidate and N-(diarylmethylene)glycinate. Among the analogs, the N-methylpyrrol-2-yl-substituted analog 1h induced the most remarkable VIE behavior in triglyceride and lipid bilayers probably due to the high π-electron-rich property of the pyrrole ring. The pyrrole substituent in imidazolone analogs can be expected to become a common template for introducing VIE behavior.


Sujet(s)
Imidazoles , Pyrroles , Pyrroles/composition chimique , Pyrroles/synthèse chimique , Viscosité , Imidazoles/composition chimique , Imidazoles/synthèse chimique , Structure moléculaire , Double couche lipidique/composition chimique , Protéines à fluorescence verte/composition chimique
8.
Molecules ; 29(12)2024 Jun 09.
Article de Anglais | MEDLINE | ID: mdl-38930816

RÉSUMÉ

3,4-Fused pyrrolocoumarins, synthetically prepared or naturally occurring, possess interesting biological properties. In this review, the synthetic strategies for the synthesis of the title compounds are presented along with their biological activities. Two routes are followed for that synthesis. In one, the pyrrole ring is formed from coumarin derivatives, such as aminocoumarins or other coumarins. In the other approach, the pyranone moiety is built from an existing pyrrole derivative or through the simultaneous formation of coumarin and pyrrole frameworks. The above syntheses are achieved via 1,3-dipolar cycloaddition reactions, Michael reaction, aza-Claisen rearrangement reactions, multi-component reactions (MCR), as well as metal-catalyzed reactions. Pyrrolocoumarins present cytotoxic, antifungal, antibacterial, α-glucosidase inhibition, antioxidant, lipoxygenase (LOX) inhibition, and fluorescent activities, as well as benzodiazepine receptor ability.


Sujet(s)
Coumarines , Pyrroles , Coumarines/composition chimique , Coumarines/synthèse chimique , Pyrroles/composition chimique , Pyrroles/synthèse chimique , Humains , Antioxydants/composition chimique , Antioxydants/synthèse chimique , Antioxydants/pharmacologie , Structure moléculaire , Réaction de cycloaddition
9.
J Inorg Biochem ; 258: 112617, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38805758

RÉSUMÉ

Four Pt(II) bis(pyrrole-imine) Schiff base chelates (1-4) were synthesised by previously reported methods, through a condensation reaction, and the novel crystal structure of 2,2'-{propane-1,3-diylbis[nitrilo(E)methylylidene]}bis(pyrrol-1-ido)platinum(II) (1) was obtained. Pt(II) complexes 1-4 exhibited phosphorescence, with increased luminescence in anaerobic solvents or when bound to human serum albumin (HSA). One of the complexes shows a 15.6-fold increase in quantum yield when bound to HSA and could be used to detect HSA concentrations as low as 5 nM. Pt(II) complexes 1-3 was investigated as potential theranostic agents in MCF-7 breast cancer cells, but only complex 3 exhibited cytotoxicity when irradiated with UV light (λ355nmExcitation). Interestingly, the cytotoxicity of complex 1 was unresponsive to UV light irradiation. This indicates that only complex 3 can be considered a potential photosensitising agent.


Sujet(s)
Pyrroles , Humains , Cellules MCF-7 , Pyrroles/composition chimique , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Bases de Schiff/composition chimique , Imines/composition chimique , Complexes de coordination/pharmacologie , Complexes de coordination/composition chimique , Complexes de coordination/effets des radiations , Complexes de coordination/synthèse chimique , Luminescents/composition chimique , Luminescents/toxicité , Luminescents/synthèse chimique , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme
10.
J Control Release ; 371: 204-215, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38810704

RÉSUMÉ

Cuproptosis, a newly discovered mechanism of inducing tumor cell death, primarily relies on the intracellular accumulation of copper ions. The utilization of Cu-based nanomaterials to induce cuproptosis holds promising prospects in future biomedical applications. However, the presence of high levels of glutathione (GSH) within tumor cells hinders the efficacy of cuproptosis. In this study, we have developed a BPTES-loaded biomimetic Cu-doped polypyrrole nanoparticles (CuP) nanosystem (PCB) for enhanced cuproptosis and immune modulation. PCB comprises an internal BPTES and CuP core and an external platelet membrane (PM) that facilitates active targeting to tumor sites following intravenous administration. Subsequently, PCB effectively suppresses glutaminase (GLS1) activity, thereby reducing GSH content. Moreover, CuP catalyze intracellular H2O2, amplifying oxidative stress while simultaneously inducing dihydrolipoyl transacetylase (DLAT) oligomerization through released Cu2+, resulting in cuproptosis. PCB not only inhibits primary tumors but also exhibits inhibitory effects on abscopal tumors. This work represents the first instance where GLS inhibition has been employed to enhance cuproptosis and immunotherapy. It also provides valuable insights into further investigations on cuproptosis.


Sujet(s)
Matériaux biomimétiques , Tumeurs du sein , Cuivre , Glutamine , Immunothérapie , Nanoparticules , Polymères , Pyrroles , Cuivre/composition chimique , Polymères/composition chimique , Nanoparticules/composition chimique , Nanoparticules/administration et posologie , Animaux , Femelle , Pyrroles/administration et posologie , Pyrroles/composition chimique , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Humains , Immunothérapie/méthodes , Lignée cellulaire tumorale , Glutamine/métabolisme , Matériaux biomimétiques/composition chimique , Matériaux biomimétiques/administration et posologie , Souris de lignée BALB C , Glutaminase/métabolisme , Glutaminase/antagonistes et inhibiteurs , Souris , Glutathion/métabolisme
11.
Bioorg Chem ; 149: 107499, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38815476

RÉSUMÉ

Janus Kinase 3 (JAK3) is important for the signaling transduction of cytokines in immune cells and is identified as potential target for treatment of rheumatoid arthritis (RA). Recently, we designed and synthesized two JAK3 inhibitors J1b and J1f, which featured with high selectivity but mild bioactivity. Therefore, in present study the structure was optimized to increase the potency. As shown in the results, most of the compounds synthesized showed stronger inhibitory activities against JAK3 in contrast to the lead compounds, among which 9a was the most promising candidate because it had the most potent effect in ameliorating carrageenan-induced inflammation of mice and exhibited low acute in vivo toxicity (MTD > 2 g/kg). Further analysis revealed that 9a was highly selective to JAK3 (IC50 = 0.29 nM) with only minimal effect on other JAK members (>3300-fold) and those kinases bearing a thiol in a position analogous to that of Cys909 in JAK3 (>150-fold). Meanwhile, the selectivity of JAK3 was also confirmed by PBMC stimulation assay, in which 9a irreversibly bound to JAK3 and robustly inhibited the signaling transduction with mild suppression on other JAKs. Moreover, it was showed that 9a could remarkably inhibited the proliferation of lymphocytes in response to concanavalin A and significantly mitigate disease severity in collagen induced arthritis. Therefore, present data indicate that compound 9a is a selective JAK3 inhibitor and could be a promising candidate for clinical treatment of RA.


Sujet(s)
Polyarthrite rhumatoïde , Janus kinase 3 , Inhibiteurs de protéines kinases , Pyrimidines , Janus kinase 3/antagonistes et inhibiteurs , Janus kinase 3/métabolisme , Polyarthrite rhumatoïde/traitement médicamenteux , Animaux , Pyrimidines/composition chimique , Pyrimidines/pharmacologie , Pyrimidines/synthèse chimique , Humains , Relation structure-activité , Souris , Inhibiteurs de protéines kinases/pharmacologie , Inhibiteurs de protéines kinases/composition chimique , Inhibiteurs de protéines kinases/synthèse chimique , Structure moléculaire , Relation dose-effet des médicaments , Pyrroles/composition chimique , Pyrroles/pharmacologie , Pyrroles/synthèse chimique , Carragénane , Mâle , Arthrite expérimentale/traitement médicamenteux , Arthrite expérimentale/induit chimiquement , Antirhumatismaux/pharmacologie , Antirhumatismaux/composition chimique , Antirhumatismaux/synthèse chimique , Simulation de docking moléculaire
12.
Org Biomol Chem ; 22(24): 4958-4967, 2024 06 19.
Article de Anglais | MEDLINE | ID: mdl-38819437

RÉSUMÉ

Development of biocompatible nanomaterials with mitochondria-targeting and multimodal therapeutic activities is important for cancer treatment. Herein, we designed and synthesized a multifunctional pyrrole-based nanomaterial with photothermal effects and mitochondria-targeting properties from polypyrrole and the pro-apoptotic peptide KLA. Different from traditional strategies for the preparation of PPy nanoparticles, we innovatively used the KLA peptide as the template and CuCl2 as the catalyst to trigger the oxidative polymerization of pyrrole for PPy-KLA-Cu nanoparticle formation. Besides, due to the presence of mixed-valence Cu(I)/Cu(II) states, PPy-KLA-Cu nanoparticles also exhibited multienzyme-like activities, such as peroxidase, ascorbate oxidase and glutathione peroxidase activities, which can be exploited to elevate the intracellular ROS level and simultaneously consume GSH in cancer cells. More importantly, the heat generated by PPy-KLA-Cu nanoparticles from NIR irradiation could enhance the nanozymatic activities for ROS elevation and increase the KLA-induced anticancer activity via mitochondrial dysfunction, realizing multimodal treatment of cancer cells with improved therapeutic efficacy.


Sujet(s)
Antinéoplasiques , Apoptose , Mitochondries , Polymères , Pyrroles , Pyrroles/composition chimique , Pyrroles/pharmacologie , Pyrroles/synthèse chimique , Mitochondries/effets des médicaments et des substances chimiques , Mitochondries/métabolisme , Humains , Polymères/composition chimique , Polymères/pharmacologie , Polymères/synthèse chimique , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Antinéoplasiques/synthèse chimique , Apoptose/effets des médicaments et des substances chimiques , Catalyse , Peptides/composition chimique , Peptides/pharmacologie , Peptides/synthèse chimique , Espèces réactives de l'oxygène/métabolisme , Cuivre/composition chimique , Cuivre/pharmacologie , Nanostructures/composition chimique , Tests de criblage d'agents antitumoraux , Lignée cellulaire tumorale , Tumeurs/traitement médicamenteux , Tumeurs/anatomopathologie
13.
PLoS One ; 19(5): e0303173, 2024.
Article de Anglais | MEDLINE | ID: mdl-38739587

RÉSUMÉ

In this study, new series of N'-(2-(substitutedphenoxy)acetyl)-4-(1H-pyrrol-1-yl)benzohydrazides (3a-j) 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-(2-(substitutedphenoxy)acetyl)benzohydrazides (5a-j) were synthesized, characterized and assessed as inhibitors of enoyl ACP reductase and DHFR. Most of the compounds exhibited dual inhibition against the enzymes enoyl ACP reductase and DHFR. Several synthesized substances also demonstrated significant antibacterial and antitubercular properties. A molecular docking analysis was conducted in order to determine the potential mechanism of action of the synthesized compounds. The results indicated that there were binding interactions seen with the active sites of dihydrofolate reductase and enoyl ACP reductase. Additionally, important structural details were identified that play a critical role in sustaining the dual inhibitory activity. These findings were useful for the development of future dual inhibitors. Therefore, this study provided strong evidence that several synthesized molecules could exert their antitubercular properties at the cellular level through multi-target inhibition. By shedding light on the mechanisms through which these compounds exert their inhibitory effects, this research opens up promising avenues for the future development of dual inhibitors with enhanced antibacterial and antitubercular properties. The study's findings underscore the importance of multi-target approaches in drug design, providing a strong foundation for the design and optimization of novel compounds that can effectively target bacterial infections at the cellular level.


Sujet(s)
Antituberculeux , Pyrroles , Dihydrofolate reductase , Humains , Antituberculeux/pharmacologie , Antituberculeux/composition chimique , Antituberculeux/synthèse chimique , Domaine catalytique , Enoyl-(acyl-carrier protein) reductase (NADH)/antagonistes et inhibiteurs , Enoyl-(acyl-carrier protein) reductase (NADH)/métabolisme , Enoyl-(acyl-carrier protein) reductase (NADH)/composition chimique , Antifoliques/pharmacologie , Antifoliques/composition chimique , Antifoliques/synthèse chimique , Tests de sensibilité microbienne , Simulation de docking moléculaire , Mycobacterium tuberculosis/effets des médicaments et des substances chimiques , Mycobacterium tuberculosis/enzymologie , Pyrroles/synthèse chimique , Pyrroles/composition chimique , Pyrroles/pharmacologie , Relation structure-activité , Dihydrofolate reductase/métabolisme , Dihydrofolate reductase/composition chimique
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124515, 2024 Oct 05.
Article de Anglais | MEDLINE | ID: mdl-38810435

RÉSUMÉ

Mirabegron (MRB) is a ß3-adrenoceptor agonist used for managing overactive bladder syndrome. A cost-effective, environmentally friendly, and highly sensitive spectrofluorimetric method was suggested to serve the purpose of quantifying MRB in its pure state, pharmaceutical tablets, spiked human plasma and urine, and testing content uniformity. In the present study, ninhydrin and phenylacetaldehyde react with the amino group moiety of MRB in Teorell-Stenhagen buffer (pH 7.5) to generate a strongly fluorescent diaryl pyrrolone compound that emits fluorescence at a wavelength of 477 nm upon excitation at 385 nm. The obtained calibration curve showed a linear relationship with a high correlation coefficient (r = 0.9997) in the concentration range of 0.25 to 5.0 µg mL-1. Limits of detection (LOD) and quantitation (LOQ) were 0.082 and 0.248 µg mL-1 respectively. The procedure was verified in accordance with the ICH guidelines. The suggested approach could be utilized for the selective analysis of MRB in its pharmaceuticals, either containing a single drug or co-formulated with solifenacin succinate. The greenness of the suggested method was confirmed using different green analytical metrics.


Sujet(s)
Acétanilides , Limite de détection , Ninhydrine , Spectrométrie de fluorescence , Thiazoles , Humains , Ninhydrine/composition chimique , Spectrométrie de fluorescence/méthodes , Acétanilides/urine , Acétanilides/sang , Acétanilides/composition chimique , Thiazoles/composition chimique , Thiazoles/urine , Thiazoles/sang , Pyrroles/composition chimique , Colorants fluorescents/composition chimique , Colorants fluorescents/synthèse chimique , Comprimés , Acétaldéhyde/analogues et dérivés
15.
Eur J Med Chem ; 273: 116470, 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38762915

RÉSUMÉ

Cancer poses a significant threat to human health. Therefore, it is urgent to develop potent anti-cancer drugs with excellent inhibitory activity and no toxic side effects. Pyrrole and its derivatives are privileged heterocyclic compounds with significant diverse pharmacological effects. These compounds can target various aspects of cancer cells and have been applied in clinical settings or are undergoing clinical trials. As a result, pyrrole has emerged as a promising drug scaffold and has been further probed to get novel entities for the treatment of cancer. This article reviews recent research progress on anti-cancer drugs containing pyrrole. It focuses on the mechanism of action, biological activity, and structure-activity relationships of pyrrole derivatives, aiming to assist in designing and synthesizing innovative pyrrole-based anti-cancer compounds.


Sujet(s)
Antinéoplasiques , Pyrroles , Pyrroles/composition chimique , Pyrroles/pharmacologie , Pyrroles/synthèse chimique , Humains , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Antinéoplasiques/synthèse chimique , Relation structure-activité , Structure moléculaire , Tests de criblage d'agents antitumoraux , Tumeurs/traitement médicamenteux , Tumeurs/anatomopathologie , Prolifération cellulaire/effets des médicaments et des substances chimiques , Animaux
16.
J Am Chem Soc ; 146(23): 16268-16280, 2024 Jun 12.
Article de Anglais | MEDLINE | ID: mdl-38810110

RÉSUMÉ

Reactive functional groups, such as N-nitrosamines, impart unique bioactivities to the natural products in which they are found. Recent work has illuminated enzymatic N-nitrosation reactions in microbial natural product biosynthesis, motivating interest in discovering additional metabolites constructed using such reactivity. Here, we use a genome mining approach to identify over 400 cryptic biosynthetic gene clusters (BGCs) encoding homologues of the N-nitrosating biosynthetic enzyme SznF, including the BGC for chalkophomycin, a CuII-binding metabolite that contains a C-type diazeniumdiolate and N-hydroxypyrrole. Characterizing chalkophomycin biosynthetic enzymes reveals previously unknown enzymes responsible for N-hydroxypyrrole biosynthesis, including the first prolyl-N-hydroxylase, and a key step in the assembly of the diazeniumdiolate-containing amino acid graminine. Discovery of this pathway enriches our understanding of the biosynthetic logic employed in constructing unusual heteroatom-heteroatom bond-containing functional groups, enabling future efforts in natural product discovery and biocatalysis.


Sujet(s)
Pyrroles , Pyrroles/métabolisme , Pyrroles/composition chimique , Famille multigénique , Streptomyces/enzymologie , Streptomyces/métabolisme , Streptomyces/génétique
17.
J Mater Chem B ; 12(24): 5898-5906, 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38779948

RÉSUMÉ

Developing synthetic materials, with enzyme-like molecular recognition capabilities, as functional receptors in electronic or electrochemical devices for the timely diagnosis of major diseases is a great challenge. Herein, we present the development of Fe/MIPpy nanozymes, characterized as enzyme-like artificial receptors, for the precise and non-invasive monitoring of cancer biomarkers in aqueous solutions and human saliva. Through the integration of PVA-stabilized FeFe2O4 nanocrystals in a molecularly imprinted conducting polypyrrole matrix, the Fe/MIPpy nanozymes demonstrate 424 nA cm-2 nM-1 sensitivity and 220 pM detection limit. Charge-transfer mechanisms, Fe/MIPpy-spermine interactions, and the principle of spermine recognition are investigated by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The disposable Fe/MIPpy sensor operates wirelessly and offers rapid and remote quantification of spermine, making it a promising material for the development of cost-effective tools for non-invasive cancer diagnosis and prognosis.


Sujet(s)
Techniques électrochimiques , Polymères , Pyrroles , Spermine , Humains , Spermine/composition chimique , Spermine/analyse , Pyrroles/composition chimique , Polymères/composition chimique , Tumeurs/diagnostic , Catalyse , Composés du fer III/composition chimique , Pronostic , Propriétés de surface , Taille de particule
18.
J Med Chem ; 67(11): 9355-9373, 2024 Jun 13.
Article de Anglais | MEDLINE | ID: mdl-38805667

RÉSUMÉ

Development of more efficacious medications with improved safety profiles to manage and treat multiple forms of pain is a critical element of healthcare. To this end, we have designed and synthesized a novel class of tetracyclic pyridopyrroloquinoxalinone derivatives with analgesic properties. The receptor binding profiles and analgesic properties of these tetracyclic compounds were studied. Systematic optimizations of this novel scaffold culminated in the discovery of the clinical candidate, (6bR,10aS)-8-[3-(4-fluorophenoxy)propyl]-6b,7,8,9,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-2(3H)-one (compound 5, ITI-333), which exhibited potent binding affinity to serotonin 5-HT2A (Ki = 8.3 nM) and µ-opioid receptors (MOR, Ki = 11 nM) and moderate affinity to adrenergic α1A (Ki = 28 nM) and dopamine D1 (Ki = 50 nM) receptors. ITI-333 acts as a 5-HT2A receptor antagonist, a MOR partial agonist, and an adrenergic α1A receptor antagonist. ITI-333 exhibited dose-dependent analgesic effects in rodent models of acute pain. Currently, this investigational new drug is in phase I clinical development.


Sujet(s)
Analgésiques , Douleur , Animaux , Humains , Analgésiques/pharmacologie , Analgésiques/composition chimique , Analgésiques/synthèse chimique , Analgésiques/usage thérapeutique , Relation structure-activité , Administration par voie orale , Douleur/traitement médicamenteux , Souris , Mâle , Rats , Découverte de médicament , Rat Sprague-Dawley , Biodisponibilité , Récepteur mu/métabolisme , Récepteur mu/agonistes , Pyridines/composition chimique , Pyridines/pharmacologie , Pyridines/synthèse chimique , Pyridines/usage thérapeutique , Pyridines/pharmacocinétique , Pyrroles/composition chimique , Pyrroles/pharmacologie , Pyrroles/synthèse chimique , Pyrroles/pharmacocinétique
19.
Bioorg Chem ; 148: 107468, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38781670

RÉSUMÉ

A new efficient and versatile one-pot three-component synthesis of substituted pyrrolo[1,2-a]thieno[3,2-e]pyrimidine derivatives has been developed. It is based on a multistep cascade reaction from 2-aminothiophenes and 2-hydroxy-4-oxobut-2-enoic acids, and derivatives of cyanoacetic acid catalyzed by diisopropylethylamine. As a result, novel pyrrolo[1,2-a]thieno[3,2-e]pyrimidine derivatives (21 compounds) were synthesized in a mild reaction conditions with a high yield. The structures of the developed compounds were confirmed by NMR and elemental analysis. The influence of electron-withdrawing or electron-donor substituents on the antitumor activity of the developed compounds has been identified. In vitro screening analysis of 21 compounds revealed six lead candidates (12aa, 12dc, 12hc, 12ic, 12lb, and 12mb) that demonstrated the most significant antitumor activity against B16-F10, 4T1 and CT26 cells. Necrosis/apoptosis assay showed that apoptosis was the predominant mechanism of cell death. Molecular docking analysis revealed several potential targets for tested compounds, i.e. phosphatidylinositol 5-phosphate 4-kinase (PI5P4K2C), proto-oncogene serine/threonine-protein kinase (Pim-1), nicotinamide phosphoribosyltransferase (NAMPT) and dihydrofolate reductase (DHFR). The lead compound (12aa) can effectively induce cell apoptosis, possesses a high yield (98 %) and requires low-cost starting chemicals for its synthesis. In vivo experiments with melanoma-bearing mice confirmed that 12aa compound resulted in the significant tumor inhibition on 15 d after the therapy. In particular, tumor volume was ∼0.19 cm3 for 50 mg/kg versus ∼2.39 cm3 in case of untreated mice and tumor weight was ∼71.6 mg for 50 mg/kg versus ∼452.4 mg when considered untreated mice. Thus, our results demonstrated the high potential of the 12aa compound in the treatment of melanoma and can be recommended for further preclinical studies.


Sujet(s)
Antinéoplasiques , Conception de médicament , Tests de criblage d'agents antitumoraux , Pyrimidines , Pyrroles , Antinéoplasiques/pharmacologie , Antinéoplasiques/synthèse chimique , Antinéoplasiques/composition chimique , Animaux , Pyrimidines/composition chimique , Pyrimidines/synthèse chimique , Pyrimidines/pharmacologie , Souris , Relation structure-activité , Structure moléculaire , Humains , Pyrroles/composition chimique , Pyrroles/pharmacologie , Pyrroles/synthèse chimique , Prolifération cellulaire/effets des médicaments et des substances chimiques , Relation dose-effet des médicaments , Lignée cellulaire tumorale , Simulation de docking moléculaire , Proto-oncogène Mas , Apoptose/effets des médicaments et des substances chimiques , Souris de lignée C57BL , Mélanome expérimental/traitement médicamenteux , Mélanome expérimental/anatomopathologie , Mélanome expérimental/métabolisme
20.
Int J Biol Macromol ; 270(Pt 2): 132491, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38763240

RÉSUMÉ

Capacitive deionization (CDI) technology holds great potential for rapid and efficient uranyl ion removal from wastewater. However, the related electrode materials still have much room for research. Herein, chitosan/phytic acid complexes were anchored on polypyrrole nanotubes (CS/PA-PPy) to fabricate the electrode for the electrosorption of uranyl ions (UO22+). In this system, polypyrrole nanotubes provided specific channels for ion and electron diffusion, and chitosan/phytic acid complexes offered selective sites for UO22+ binding. The results demonstrated that CS/PA-PPy via electrosorption showed faster kinetics and higher uranium uptake than those via physicochemical adsorption. The maximum adsorption capacity toward UO22+ via electrosorption (1.2 V) could reach 799.3 mg g-1, which was higher than most of the reported CDI electrodes. Electrochemical measurements and experimental characterizations showed that the electrosorption of UO22+ by CS/PA-PPy was a synergistic effect of capacitive process and physicochemical adsorption, in which the capacitive mechanism involved the formation of an electric double layer from hollow polypyrrole nanotubes, whereas the coordination of phosphate, amino and hydroxyl groups with UO22+ was attributed to physicochemical adsorption. With the rational design of material, along with its excellent uranium removal performance, this work exhibited a novel and potential composite electrode for uranium capture via CDI from wastewater.


Sujet(s)
Chitosane , Électrodes , Nanotubes , Polymères , Pyrroles , Uranium , Eaux usées , Uranium/composition chimique , Uranium/isolement et purification , Polymères/composition chimique , Eaux usées/composition chimique , Pyrroles/composition chimique , Nanotubes/composition chimique , Adsorption , Chitosane/composition chimique , Purification de l'eau/méthodes , Cinétique
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