RESUMO
A new series of benzene-sulfonamide derivatives 3a-i was designed and synthesized via the reaction of N-(pyrimidin-2-yl)cyanamides 1a-i with sulfamethazine sodium salt 2 as dual Src/Abl inhibitors. Spectral data IR, 1H-, 13C- NMR and elemental analyses were used to confirm the structures of all the newly synthesized compounds 3a-i and 4a-i. Crucially, we screened all the synthesized compounds 3a-i against NCI 60 cancer cell lines. Among all, compound 3b was the most potent, with IC50 of 0.018 µM for normoxia, and 0.001 µM for hypoxia, compared to staurosporine against HL-60 leukemia cell line. To verify the selectivity of this derivative, it was assessed against a panel of tyrosine kinase EGFR, VEGFR-2, B-raf, ERK, CK1, p38-MAPK, Src and Abl enzymes. Results revealed that compound 3b can effectively and selectively inhibit Src/Abl with IC500.25 µM and Abl inhibitory activity with IC500.08 µM, respectively, and was found to be more potent on these enzymes than other kinases that showed the following results: EGFR IC500.31 µM, VEGFR-2 IC500.68 µM, B-raf IC500.33 µM, ERK IC501.41 µM, CK1 IC500.29 µM and p38-MAPK IC500.38 µM. Moreover, cell cycle analysis and apoptosis performed to compound 3b against HL-60 suggesting its antiproliferative activity through Src/Abl inhibition. Finally, molecular docking studies and physicochemical properties prediction for compounds 3b, 3c, and 3 h were carried out to investigate their biological activities and clarify their bioavailability.
Assuntos
Antineoplásicos , Proliferação de Células , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-abl , Quinases da Família src , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Guanidina/farmacologia , Guanidina/química , Guanidina/síntese química , Guanidina/análogos & derivados , Células HL-60 , Leucemia/tratamento farmacológico , Leucemia/patologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-abl/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-abl/metabolismo , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/metabolismo , Relação Estrutura-Atividade , Cianamida/síntese química , Cianamida/química , Cianamida/farmacologiaRESUMO
The inclination toward natural products has led to the onset of the discovery of new bioactive metabolites that could be targeted for specific therapeutic or agronomic applications. Despite increasing knowledge coming to light of plant-derived materials as leads for new herbicides, relatively little is known about the mode of action on herbicide-resistant weeds. Cyanamide (CA) is a naturally occurring herbicide synthesized by hairy vetch (Vicia villosa Roth.). However, it has not been experimentally verified whether CA suppresses target plants via sustained discharge at low concentrations, as is often the case with most plant-derived materials. This study aimed to detect the toxicity and the mode of action of CA to alfalfa (Medicago sativa L.) and redroot pigweed (Amaranthus retroflexus L.). The toxicity of CA toward the alfalfa and redroot pigweed by three different exposure patterns was compared: low-concentration repeated exposure with 0.3 g/L CA (LRE), high-concentration single exposure with 1.2 g/L CA (HSE), and distilled water spray as control. The results showed that CA had a stronger inhibitory effect on redroot pigweed growth compared to alfalfa under both LRE and HSE exposure modes, with leaves gradually turning yellow and finally wilting. Beyond that, field trials were conducted to corroborate the toxicity of CA to alfalfa and redroot pigweed. The results have also shown that CA could inhibit the growth of redroot pigweed without significant adverse effects on alfalfa. The outcomes concerning electrolyte permeability, root activity, and malondialdehyde (MDA) content indicated that CA suppressed the growth of redroot pigweed by interfering with the structure of the cell membrane and impacting cellular osmotic potential. CA could destroy the cell membrane structure to inhibit the growth of the redroot pigweed by both LRE and HSE exposure modes, which provides a theoretical basis for preventing and controlling redroot pigweed in alfalfa fields.
Assuntos
Amaranthus , Cianamida , Herbicidas , Medicago sativa , Medicago sativa/efeitos dos fármacos , Herbicidas/toxicidade , Herbicidas/farmacologia , Amaranthus/efeitos dos fármacos , Cianamida/farmacologia , Malondialdeído/metabolismo , Plantas Daninhas/efeitos dos fármacosRESUMO
A trinuclear Zn (II) complex, [(ZnL{N(CN)2})2Zn], termed complex 1 has been synthesized by the reaction of an aqueous solution of sodium dicyanamide to the methanolic solution of Zn (CH3COO)2, 2H2O and corresponding Schiff base (H2L) which is derived from 1:2 condensation of 1, 4 butane diamine with 3-ethoxy salicylaldehyde. Complex 1 is characterized by elemental analysis, IR, UV and Single X-ray diffraction study. Drug resistance is a growing global public health concern that has prompted researchers to look into advanced alternative treatment modalities. In this context, complex 1 has shown promising antibacterial and antibiofilm efficacy against gram-positive Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus strains. Complex 1 attenuated Staphylococcal biofilm formation by reducing several virulence factors including the formation of extracellular polysaccharide matrix, slime, haemolysin, staphyloxanthin, auto-aggregation, cell surface hydrophobicity, and motility. Notably, complex 1 mechanistically potentiated Reactive Oxygen Species (ROS) generation within the bacterial cells, leading to the damage of bacterial cell membrane followed by DNA leakage and thereby impeding the growth of Staphylococcus aureus. Furthermore, complex 1 significantly exhibited anticancer activity by reducing the growth of prostate adenocarcinoma cells. It obstructed the migration of cancer cells by potentiating apoptosis and arresting the cell cycle at the G2/M phase. In summary, complex 1 could act as a potent candidate for the generation of novel antibacterial, antibiofilm as well as anticancer treatment regimens for the management of drug-resistant biofilm-mediated Staphylococcus aureus infection and lethal prostate malignancy.
Assuntos
Cianamida , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Masculino , Humanos , Espécies Reativas de Oxigênio , Bases de Schiff/farmacologia , Antibacterianos/farmacologia , Staphylococcus aureus , Biofilmes , Bactérias , Infecções Estafilocócicas/microbiologia , Zinco/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Hydrogen cyanamide is a plant growth regulator introduced in Italy as Dormex in 2000, but recalled from the market in 2008. It's currently not authorized in Europe. Inhalation/dermal contact may cause irritation/caustic burns, ingestion of severe organ damage and concomitant alcohol consumption disulfiram-like reaction due to aldehyde-dehydrogenase inhibition by hydrogen cyanamide. AIMS: To study all exposure cases referred to our centre, evaluating temporal and geographic distribution and analysing clinical manifestations, including the ones after alcohol consumption. METHODS: We retrospectively evaluated all hydrogen cyanamide exposures referred to our Poison Control Centre (January 2007-December 2021). For each case, age, sex, exposure route/year, geographical location, intent of exposure, alcohol co-ingestion, emergency department-admission Poison Severity Score, signs/symptoms and treatment were analysed. RESULTS: Thirty subjects were included. Median case/year was 1 [1; 2]: 79% occurred after market withdrawal, 92% in Sicily. All exposures were unintentional and work related; 41% of patients also co-ingested alcohol. Mean poison severity score at emergency department admission was 1.54, more severe when ingestion occurred. The most common signs/symptoms were flushing, secondary to peripheral vasodilation (41%), hyperaemia/erythema (29%), dyspnoea (25%), nausea (20%), vomiting (12%), oedema (12%), II-III degrees burns (12%) and pharyngodynia (12%). All patients were treated symptomatically and fully recovered. CONCLUSIONS: Hydrogen cyanamide exposure can lead to severe clinical manifestations. Despite its withdrawal from the Italian market, hydrogen cyanamide is still used: through PCC's crucial role in monitoring exposure to agricultural products efforts should be made to contrast illegal trade and increase awareness of its potential toxicity in those countries in which it's still legal.
Assuntos
Queimaduras , Venenos , Humanos , Centros de Controle de Intoxicações , Cianamida/efeitos adversos , Estudos RetrospectivosRESUMO
The commonly used expression systems in Saccharomyces cerevisiae typically rely on either constitutive or galactose-regulated promoters. The lack of inducible systems in S. cerevisiae limits the precise temporal regulation of protein function and yeast metabolism. We herein repurposed the galactose-regulated system to make it respond to cyanamide. By using a cyanamide-inducible DDI2 promoter to control Gal4 expression in CEN.PK2-1C with Δgal80, a tight and graded cyanamide-inducible GAL system with an enhanced signal output was constructed. Subsequently, we demonstrated that the cyanamide-inducible GAL system was capable of tightly regulating the pentafunctional Aro1 protein to achieve conditional shikimate pathway activity. Taken together, the cyanamide-inducible GAL system could be implemented for both fundamental research and applied biotechnology.
Assuntos
Cianamida , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Cianamida/farmacologia , Galactose , RegulonRESUMO
Benzodiazaborines (BDABs) have emerged as a valuable tool to produce stable and functional bioconjugates via a click-type transformation. However, the current available methods to install them on peptides lack bioorthogonality, limiting their applications. Here, we report a strategy to install BDABs directly on peptide chains using (2-cyanamidophenyl)boronic acids (2CyPBAs). The resulting BDAB is stabilized through the formation of a key intramolecular B-N bond. This technology was applied in the selective modification of N-terminal cysteine-containing functional peptides.
Assuntos
Ácidos Borônicos , Cisteína , Ácidos Borônicos/química , Cisteína/química , Peptídeos/química , Nitrilas/química , Cianamida/químicaRESUMO
This work describes the unprecedented intramolecular cyclization occurring in a set of α-azido-ω-isocyanides in the presence of catalytic amounts of sodium azide. These species yield the tricyclic cyanamides [1,2,3]triazolo[1,5-a]quinoxaline-5(4H)-carbonitriles, whereas in the presence of an excess of the same reagent, the azido-isocyanides convert into the respective C-substituted tetrazoles through a [3 + 2] cycloaddition between the cyano group of the intermediate cyanamides and the azide anion. The formation of tricyclic cyanamides has been examined by experimental and computational means. The computational study discloses the intermediacy of a long-lived N-cyanoamide anion, detected by NMR monitoring of the experiments, subsequently converting into the final cyanamide in the rate-determining step. The chemical behavior of these azido-isocyanides endowed with an aryl-triazolyl linker has been compared with that of a structurally identical azido-cyanide isomer, experiencing a conventional intramolecular [3 + 2] cycloaddition between its azido and cyanide functionalities. The synthetic procedures described herein constitute metal-free approaches to novel complex heterocyclic systems, such as [1,2,3]triazolo[1,5-a]quinoxalines and 9H-benzo[f]tetrazolo[1,5-d][1,2,3]triazolo[1,5-a][1,4]diazepines.
Assuntos
Azidas , Cianetos , Azidas/química , Ciclização , Estrutura Molecular , Cianamida , Quinoxalinas/químicaRESUMO
Hydrogen cyanamide (Dormex) is a plant growth regulator that is classified as a highly toxic poison. There are no definite investigations to help in its diagnosis and follow-up. This study aimed to investigate the role of hypoxia-inducible factor-1α (HIF-1α) in the diagnosis, prediction, and follow-up of Dormex-intoxicated patients. Sixty subjects were equally divided into two groups: group A, the control group, and group B, the Dormex group. Clinical and laboratory evaluations, including arterial blood gases (ABG), prothrombin concentration (PC), the international normalized ratio (INR), a complete blood count (CBC), and HIF-1α, were done on admission. CBC and HIF-1α were repeated for group B 24 and 48 h after admission to track abnormalities. Group B also had brain computed tomography (CT). Patients with abnormal CT scans were referred for brain magnetic resonance imaging (MRI). Significant differences in levels of HB, WBCs, and platelets were also detected in group B up to 48 h after admission, as white blood cells (WBCs) rose with time and hemoglobin (HB) and platelets diminished. The results described a highly significant difference in HIF-1α between the groups, and it depended on the clinical condition; therefore, it can be used in the prediction and follow-up of patients up to 24 h after admission.
Assuntos
Cianamida , Subunidade alfa do Fator 1 Induzível por Hipóxia , Humanos , HipóxiaRESUMO
Calcium cyanamide (CaCN2) has been used in agriculture for more than a century as a nitrogen fertilizer with nitrification inhibiting and pest-controlling characteristics. However, in this study, a completely new application area was investigated, as CaCN2 was used as a slurry additive to evaluate its effect on the emission of ammonia and greenhouse gases (GHG) consisting of methane, carbon dioxide, and nitrous oxide. Efficiently reducing these emissions is a key challenge facing the agriculture sector, as stored slurry is a major contributor to global GHG and ammonia emissions. Therefore, dairy cattle and fattening pig slurry was treated with either 300 mg kg-1 or 500 mg kg-1 cyanamide formulated in a low-nitrate CaCN2 product (Eminex®). The slurry was stripped with nitrogen gas to remove dissolved gases and then stored for 26 weeks, during which gas volume and concentration were measured. Suppression of methane production by CaCN2 began within 45 min after application and persisted until the storage end in all variants, except in the fattening pig slurry treated with 300 mg kg-1, in which the effect faded after 12 weeks, indicating that the effect is reversible. Furthermore, total GHG emissions decreased by 99% for dairy cattle treated with 300 and 500 mg kg-1 and by 81% and 99% for fattening pig, respectively. The underlying mechanism is related to CaCN2-induced inhibition of microbial degradation of volatile fatty acids (VFA) and its conversion to methane during methanogenesis. This increases the VFA concentration in the slurry, lowering its pH and thereby reducing ammonia emissions.
Assuntos
Gases , Gases de Efeito Estufa , Bovinos , Animais , Suínos , Amônia/análise , Cianamida , Metano/análise , Esterco/análise , Nitrogênio , Óxido Nitroso/análiseRESUMO
An unprecedented DMAP-catalysed amidation of aryl and alkyl carboxylic acids with organo-cyanamides has been developed. Unlike the use of N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS) as an electrophilic cyanating reagent, an unusual desulfonylation/decyanation reaction model has been disclosed for the first time. Remarkable features of this reaction include readily available substrates, simple operation and broad scope, enabling the efficient synthesis of structurally diverse amides. The synthetic utility of this protocol was demonstrated by the late-stage amidation of bioactive carboxylic acids and a scale-up reaction.
Assuntos
Ácidos Carboxílicos , Cianamida , Indicadores e Reagentes , Estrutura Molecular , AmidasRESUMO
Transcriptional enhanced associate domains (TEADs) are transcription factors that bind to cotranscriptional activators like the yes-associated protein (YAP) or its paralog transcriptional coactivator with a PDZ-binding motif (TAZ). TEAD·YAP/TAZ target genes are involved in tissue and immune homeostasis, organ size control, tumor growth, and metastasis. Here, we report isoindoline and octahydroisoindole small molecules with a cyanamide electrophile that forms a covalent bond with a conserved cysteine in the TEAD palmitate-binding cavity. Time- and concentration-dependent studies against TEAD1-4 yielded second-order rate constants kinact/KI greater than 100 M-1 s-1. Compounds inhibited YAP1 binding to TEADs with submicromolar IC50 values. Cocrystal structures with TEAD2 enabled structure-activity relationship studies. In mammalian cells, compounds suppressed CTGF mRNA levels and inhibited TEAD1-4 transcriptional activity with submicromolar IC50 values. Inhibition of TEAD binding to YAP1 in mammalian cells was also observed. Several compounds inhibited the cell viability of sarcoma, hepatocellular carcinoma, glioblastoma, and breast cancer cells with single-digit micromolar IC50 values.
Assuntos
Cianamida , Neoplasias , Animais , Humanos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Sinalização YAP , Fatores de Transcrição/metabolismo , Mamíferos/metabolismoRESUMO
Two florescent xanthene-cyanamide lysosomal trackers emitting strongly at â¼525â nm were prepared from fluorescein and rhodol methyl esters in microwave-assisted reactions. Both forms named "off" (nonfluorescent lactam) and "on" (strongly fluorescent ring-opened amide) have been comprehensively characterized out by using a combination of NMR spectroscopy, X-ray analysis, fluorimetry and confocal microscopy. Known rhodamines bearing electron-withdrawing groups (EWGs) exhibit an equilibrium between non-fluorescent (off) and fluorescent (on) depending on the dielectric constant of the medium. Here, cyanamide was introduced as EWG amine into the fluorescein and rhodol framework. Unlike rhodamine-type dyes, the ring-opened forms of fluorescein- and rhodol-cyanamides are stable in protic solvents under circumneutral and basic pH conditions. The osteoblastic cell line MC3T3-E1 from C57BL/6 mouse calvaria was used for confocal imaging where the different organelles and nuclei were distinguished by using an orthogonal combination of fluorescent dyes.
Assuntos
Cianamida , Corantes Fluorescentes , Camundongos , Animais , Camundongos Endogâmicos C57BL , Corantes Fluorescentes/química , Rodaminas/química , Fluoresceína , LisossomosRESUMO
The inclination toward natural products has led to the onset of the discovery of new bioactive metabolites that could be targeted for specific therapeutic or agronomic applications. Despite increasing knowledge coming to light of allelochemicals as leads for new herbicides, relatively little is known about the mode of action of allelochemical-based herbicides on herbicide-resistant weeds. Cyanamide is an allelochemical produced by hairy vetch (Vicia villosa Roth.). This study aimed to detect the toxicity of cyanamide to alfalfa and amaranth. Seed germination experiments were carried out by the filter paper culture, and the seedling growth inhibition experiment was carried out by spraying alfalfa (Medicago sativa L.) and amaranth (Amaranthus retroflexus L.) seedlings with cyanamide. The results showed that when the concentration of cyanamide was 0.1 g·L-1, the germination of amaranth seeds could be completely inhibited without affecting the germination of alfalfa seeds. At the concentration of 0.5 g·L-1, cyanamide could significantly inhibit the growth of the root and stem of amaranth seedlings but did not affect the growth of alfalfa. This effect was associated with the induction of oxidative stress. The ascorbate peroxidase (APX) and catalase (CAT) activity of amaranth decreased by 6.828 U/g FW and 290.784 U/g FW, respectively. The malondialdehyde (MDA) content, peroxidase (POD), and superoxide dismutase (SOD) activity of amaranth firstly increased and then decreased with the increasing concentration of CA. These enzyme activities of amaranth changed more than that of alfalfa. Activities of the antioxidant enzymes APX, CAT, POD, and SOD and the content of MDA varied dramatically, thereby demonstrating the great influence of reactive oxygen species upon identified allelochemical exposure. In addition, cyanamide can also inhibit the production of chlorophyll, thereby affecting the growth of plants. From the above experiments, we know that cyanamide can inhibit the growth of amaranth in alfalfa fields. Thus, the changes caused by cyanamide described herein can contribute to a better understanding of the actions of allelochemical and the potential use of cyanamide in the production of bioherbicides.
Assuntos
Amaranthus , Herbicidas , Medicago sativa , Cianamida , Amaranthus/metabolismo , Plântula , Germinação , Ascorbato Peroxidases/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Peroxidase/metabolismo , Peroxidases , Feromônios/farmacologia , Superóxido Dismutase/metabolismo , Herbicidas/toxicidadeRESUMO
We report herein the dielectric properties response of two ionic chitosan derivatives. More specifically, we report here chitosan derivatives bearing guanidinium groups, prepared through the reaction between chitosan and cyanamide when scandium (III) triflate is present. The anionic counter ions of the guanidinium groups could be changed by working either in acetic acid or hydrochloric acid. In this way, two chitosan derivatives, namely N-guanidinium chitosan acetate (GChAc) and N-guanidinium chitosan chloride (GChCl), were produced. The materials were investigated by 13C solid state NMR, FT-IR spectroscopy, SEM and TEM analysis and compared with the parent chitosan. Dielectric spectroscopy has been used to study the relaxation behavior of the parent chitosan and the new chitosan derivatives over wide ranges of temperature and frequency, indicating that local motion is affected by counter ions. Due to these features, these materials are interesting candidates as high-power electrical materials for green technological applications.
Assuntos
Quitosana , Quitosana/química , Cloretos , Cianamida , Guanidina/química , Ácido Clorídrico , Escândio , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The rapid synthesis of diverse substituted polycyclic quinazolinones was achieved by two orthogonal Ugi four-component reaction (Ugi-4CR)-based protocols: the first two-step approach via an ammonia-Ugi-4CR followed by palladium-catalyzed annulation; in the second approach, cyanamide was used unprecedently as an amine component in Ugi-4CR followed by an AIBN/tributyltin hydride-induced radical reaction. Like no other method, MCR and cyclization could efficiently construct many biologically interesting compounds with tailored properties in very few steps.
Assuntos
Paládio , Quinazolinonas , Aminas , Amônia , CianamidaRESUMO
Synthesis of novel 2-(het)aryl-substituted thiazolo-fused six- and seven-membered heterocycles, such as thiazolo[4,5-b]pyridin-5(4H)-ones, thiazolo[4,5-c]isoquinolin-5(4H)-ones, thiazolo[4,5-b]quinolin-9(4H)-ones, 4H-benzo[e]thiazolo[4,5-b]azepine-5,10-diones, have been developed in a single-pot operation via intramolecular heteroannulation of in-situ-generated 2-(het)aryl-4-amino-5-functionalized thiazoles. These 4-amino-5-functionalized thiazoles were readily obtained in a one-pot process by treatment of a range of (het)aryldithioesters with cyanamide in the presence of NaH, followed by in situ S-alkylation-intramolecular condensations of the resulting thioimidate salts with appropriate activated methylene halides. On the other hand, the corresponding 4H-benzo[b]thiazolo[4,5-e][1,4]diazepin-10(9H)-ones were synthesized in a two-step process, requiring prior isolation of 5-carboethoxy-4-(2-nitrophenyl)aminothiazoles and their subsequent reductive cyclization. The activated methylene halides employed in these reactions for the synthesis of various thiazolo-fused heterocycles were methyl bromocrotonate, ethyl 2-(bromomethyl)benzoate, 2-fluorophenacyl bromides, ethyl 2-(2-bromoacetyl)benzoate, and ethyl bromoacetate. Several of these thiazolo-fused heterocycles display yellow green to green fluorescence, and their absorption and emission spectra have also been examined.
Assuntos
Nitrogênio , Tiazóis , Azepinas , Benzoatos , Brometos , Cianamida , SaisRESUMO
Fusarium and phenolic acids in apple replant soil have deleterious effects on soil, which affects the growth of young replanted apple trees. Here, we studied the effects of different chemical fumigants (metham sodium, dazomet, calcium cyanamide, 1,3-dichloropropene, and methyl bromide) on Fusarium and phenolic acids in soil. The chemical fumigants disturbed the apple replant soil microbial community to different degrees in the order from highest to the lowest as methyl bromide > 1,3-dichloropropene > dazomet > metham sodium > calcium cyanamide. Compared with the control, the total numbers of Operational Taxonomic Unit (OTU) were 104.63 % and 9.38 % lower in the methyl bromide and calcium cyanamide treatments, respectively while the average contents of Fusarium were 88.04 % and 59.18% lower in these treatments, respectively. Higher disturbance degrees resulted in a slower recovery rate of the soil microbial community, which facilitated the transformation of the soil into a disease-suppressing state. During the recovery process, the roots recruited Streptomyces OTU2796 and Bacillus OTU2243, which alleviated Fusarium-induced stress via the synthesis of polyketones and macrolides. The roots also recruited Sphingomonas OTU3488, OTU5572, and OTU8147, which alleviated phenolic acid-induced stress through the degradation of benzoate and polycyclic aromatic hydrocarbons.
Assuntos
Fusarium , Malus , Microbiota , Praguicidas , Hidrocarbonetos Policíclicos Aromáticos , Compostos Alílicos , Cianamida , Hidrocarbonetos Bromados , Hidrocarbonetos Clorados , Hidroxibenzoatos , Macrolídeos , Praguicidas/química , Solo , Tiadiazinas , TiocarbamatosRESUMO
4-Acyl-1H-pyrrole-2,3-diones fused at [e]-side with a heterocyclic moiety are suitable platforms for the development of a hetero-Diels-Alder-reaction-based, diversity-oriented approaches to series of skeletally diverse heterocycles. These platforms are known to react as oxa-dienes with dienophiles to form angular 6/6/5/6-tetracyclic alkaloid-like heterocycles and are also prone to decarbonylation at high temperatures resulting in generation of acyl(imidoyl)ketenes, bidentate aza- and oxa-dienes, which can react with dienophiles to form skeletally diverse products (angular tricyclic products or heterocyclic ensembles). Based on these features, we have developed an approach to two series of skeletally diverse 4H-1,3-oxazines (tetracyclic alkaloid-like 4H-1,3-oxazines and 5-heteryl-4H-1,3-oxazines) via a hetero-Diels-Alder reaction of 4-acyl-1H-pyrrole-2,3-diones fused at [e]-side with cyanamides. The products of these transformations are of interest for drug discovery, since compounds bearing 4H-1,3-oxazine moiety are extensively studied for inhibitory activities against anticancer targets.
Assuntos
Cianamida , Oxazinas , Reação de Cicloadição , Descoberta de Drogas , PirróisRESUMO
Nitrogen-doped porous carbons have emerged as promising electrode materials for supercapacitors. However, the precise control of carbon geometry and the effective doping method remain challenging. Herein, a confined self-assembly template and in-situ mild activation strategy is proposed to prepare cubic lignin composite precursor, followed by co-pyrolysis with melamine at a high temperature for nitrogen-doped hierarchical porous carbons (N-HPLCs). The zinc oxalate template has the coupling effect of confinement and mild activation during carbonization, which not only prevents the restacking of the carbon matrix but also generates zinc cyanamide intermediate to avoid excessive loss of nitrogen species. The optimized N-HPLCs exhibit an accordion-like framework with interconnected porous sheets, ultrahigh edge-nitrogen doping level (up to 12.20 at.%), and a total nitrogen doping level of 14.09 at.%. Consequently, it shows a high gravimetric capacitance of 354 F/g at 0.2 A/g, an extraordinary surface-area-normalized capacitance of 82.1 ± 0.2 µF/cm2, and good rate capability in supercapacitor applications. Moreover, the fabricated coin-type symmetric supercapacitor displays a high energy density of 12.9 Wh/kg at 161.9 W/kg and superior cycling stability with a 99.5% capacitance retention after 16,000 cycles at 2.0 A/g. This work offers a novel method for preparing nitrogen-enriched lignin-derived carbon for high-performance supercapacitors.
Assuntos
Carbono , Nitrogênio , Cianamida , Lignina , Oxalatos , Porosidade , ZincoRESUMO
The zebrafish model was used to evaluate the antioxidant properties of cyanidin-3-O-glucoside (C3G) and its metabolite protocatechuic acid (PCA) against aflatoxin B1 (AFB1)-induced hepatotoxicity and oxidative stress. In this study, zebrafish larvae were cultured for 3 days post fertilization (dpf) and then induced with AFB1. After induced 4 h, 8 h, 12 h, and 24 h, 5 µg/mL C3G/PCA was added and then co-cultured to 5 dpf, respectively. The experiments showed that C3G/PCA suppressed AFB1-induced zebrafish liver atrophy and delayed the absorption of the yolk sac. In addition, reactive oxygen species (ROS) and cell death were also significantly decreased by 5 µg/mL C3G/PCA (P Ë 0.05). C3G/PCA significantly reduced hepatic biomarkers in the serum contents (P Ë 0.05). Besides, glutathione (GSH) contents were significantly upregulated, and the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly elevated in zebrafish (P Ë 0.05). The addition of 5 µg/mL C3G/PCA was capable of reducing the apoptotic levels of caspase-9 and caspase-3 after 100 ng/mL AFB1 intoxication. In conclusion, these results suggested that C3G and its metabolite PCA might antagonize the hepatotoxicity of AFB1, reduce oxidative damage and inhibit cell death.