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1.
Molecules ; 26(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34443446

RESUMO

A novel series of proflavine ureas, derivatives 11a-11i, were synthesized on the basis of molecular modeling design studies. The structure of the novel ureas was obtained from the pharmacological model, the parameters of which were determined from studies of the structure-activity relationship of previously prepared proflavine ureas bearing n-alkyl chains. The lipophilicity (LogP) and the changes in the standard entropy (ΔS°) of the urea models, the input parameters of the pharmacological model, were determined using quantum mechanics and cheminformatics. The anticancer activity of the synthesized derivatives was evaluated against NCI-60 human cancer cell lines. The urea derivatives azepyl 11b, phenyl 11c and phenylethyl 11f displayed the highest levels of anticancer activity, although the results were only a slight improvement over the hexyl urea, derivative 11j, which was reported in a previous publication. Several of the novel urea derivatives displayed GI50 values against the HCT-116 cancer cell line, which suggest the cytostatic effect of the compounds azepyl 11b-0.44 µM, phenyl 11c-0.23 µM, phenylethyl 11f-0.35 µM and hexyl 11j-0.36 µM. In contrast, the novel urea derivatives 11b, 11c and 11f exhibited levels of cytotoxicity three orders of magnitude lower than that of hexyl urea 11j or amsacrine.


Assuntos
Entropia , Proflavina/síntese química , Ureia/síntese química , Fenômenos Químicos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Cinética , Masculino , Modelos Moleculares , Proflavina/química , Proflavina/farmacologia , Ureia/química , Ureia/farmacologia
2.
Int J Biol Macromol ; 185: 543-550, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34197857

RESUMO

Controlled or slow release fertilizers have been recommended to enhance crop yield, while minimizing environmental and economic issues related from current fertilizer applications. However, alternative biodegradable and non-toxic coating material should be suggested to produce biocoated fertilizers. Here we propose the use of lignin and poly(vinyl acetate) (PVAc) as biocoating materials for preparing slow release urea fertilizer. The blend of PVAc and lignin at a mass ratio of 75:25 improved the characteristics of the formed film and increased the nitrogen release time if compared to the pure polymers. The nitrogen release time from urea granules coated with a polymeric layer of 154.3 ±â€¯5.5 µm formed by lignin and PVAc was 36 times greater than from bare urea. The increase in the polymeric coating from 52.6 ±â€¯5.2 to 80.2 ±â€¯6.1 µm decreased the curvature of the nitrogen release data by a factor of at least 1.7, while the curvature was decreased in at least 1.3 with the increase in the polymeric coating from 80.2 ±â€¯6.1 to 158.9 ±â€¯10.6 µm. The adjustment of nitrogen release data to the Peppas-Sahlin model indicated the Fickian diffusion is more predominant than relaxation contributions, since the used polymers did not present considerable swelling. Thus, the blending of PVAc and lignin at 25 wt% of lignin and 75 wt% of PVAc is suggested as a biocoating material for producing slow release fertilizers.


Assuntos
Lignina/química , Nitrogênio/química , Polivinil/química , Composição de Medicamentos , Fertilizantes , Ureia/química
3.
Molecules ; 26(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201326

RESUMO

The development of cancer treatments requires continuous exploration and improvement, in which the discovery of new drugs for the treatment of cancer is still an important pathway. In this study, based on the molecular hybridization strategy, a new structural framework with an N-aryl-N'-arylmethylurea scaffold was designed, and 16 new target compounds were synthesized and evaluated for their antiproliferative activities against four different cancer cell lines A549, MCF7, HCT116, PC3, and human liver normal cell line HL7702. The results have shown seven compounds with 1-methylpiperidin-4-yl groups having excellent activities against all four cancer cell lines, and they exhibited scarcely any activities against HL7702. Among them, compound 9b and 9d showed greatly excellent activity against the four kinds of cells, and the IC50 for MCF7 and PC3 cell lines were even less than 3 µM.


Assuntos
Antineoplásicos/química , Antineoplásicos/síntese química , Ureia/química , Ureia/síntese química , Células A549 , Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Células HCT116 , Humanos , Células PC-3 , Relação Estrutura-Atividade , Ureia/farmacologia
4.
Molecules ; 26(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208392

RESUMO

Lyocell fabrics are widely applied in textiles, however, its high flammability increases the risk of fire. Therefore, to resolve the issue, a novel biomass-based flame retardant with phosphorus and nitrogen elements was designed and synthesized by the reaction of arginine with phosphoric acid and urea. It was then grafted onto the lyocell fabric by a dip-dry-cure technique to prepare durable flame-retardant lyocell fabric (FR-lyocell). X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR) analysis demonstrated that the flame retardant was successfully introduced into the lyocell sample. Thermogravimetric (TG) and Raman analyses confirmed that the modified lyocell fabric featured excellent thermal stability and significantly increased char residue. Vertical combustion results indicated that FR-lyocell before and after washing formed a complete and dense char layer. Thermogravimetric Fourier-transform infrared (TG-FTIR) analysis suggested that incombustible substances (such as H2O and CO2) were produced and played a significant fire retarding role in the gas phase. The cone calorimeter test corroborated that the peak of heat release rate (PHRR) and total heat release (THR) declined by 89.4% and 56.4%, respectively. These results indicated that the flame retardancy of the lyocell fabric was observably ameliorated.


Assuntos
Arginina/química , Retardadores de Chama/síntese química , Ácidos Fosfóricos/química , Têxteis/análise , Ureia/química , Animais , Calorimetria/métodos , Temperatura Alta , Espectroscopia Fotoeletrônica/métodos , Fenômenos Físicos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
5.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207146

RESUMO

Human phenylalanine hydroxylase (PAH) is a metabolic enzyme involved in the catabolism of L-Phe in liver. Loss of conformational stability and decreased enzymatic activity in PAH variants result in the autosomal recessive disorder phenylketonuria (PKU), characterized by developmental and psychological problems if not treated early. One current therapeutic approach to treat PKU is based on pharmacological chaperones (PCs), small molecules that can displace the folding equilibrium of unstable PAH variants toward the native state, thereby rescuing the physiological function of the enzyme. Understanding the PAH folding equilibrium is essential to develop new PCs for different forms of the disease. We investigate here the urea and the thermal-induced denaturation of full-length PAH and of a truncated form lacking the regulatory and the tetramerization domains. For either protein construction, two distinct transitions are seen in chemical denaturation followed by fluorescence emission, indicating the accumulation of equilibrium unfolding intermediates where the catalytic domains are partly unfolded and dissociated from each other. According to analytical centrifugation, the chemical denaturation intermediates of either construction are not well-defined species but highly polydisperse ensembles of protein aggregates. On the other hand, each protein construction similarly shows two transitions in thermal denaturation measured by fluorescence or differential scanning calorimetry, also indicating the accumulation of equilibrium unfolding intermediates. The similar temperatures of mid denaturation of the two constructions, together with their apparent lack of response to protein concentration, indicate the catalytic domains are unfolded in the full-length PAH thermal intermediate, where they remain associated. That the catalytic domain unfolds in the first thermal transition is relevant for the choice of PCs identified in high throughput screening of chemical libraries using differential scanning fluorimetry.


Assuntos
Fenilalanina Hidroxilase/química , Desnaturação Proteica , Dobramento de Proteína , Sítios de Ligação , Varredura Diferencial de Calorimetria , Domínio Catalítico , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Fenilalanina Hidroxilase/isolamento & purificação , Fenilcetonúrias , Conformação Proteica , Desnaturação Proteica/efeitos dos fármacos , Dobramento de Proteína/efeitos dos fármacos , Estabilidade Proteica , Temperatura , Termodinâmica , Ureia/química
6.
Clin Drug Investig ; 41(7): 647-652, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34097256

RESUMO

BACKGROUND AND OBJECTIVE: Omecamtiv mecarbil (OM) is a novel cardiac myosin activator in development for the treatment of heart failure with reduced ejection fraction. The objective of this study was to evaluate the potential for OM to affect the pharmacokinetics of metformin. METHODS: This was an open-label, fixed-sequence study in 14 healthy subjects. On Day 1, subjects received an 850 mg oral dose of metformin. From Days 4 to 9, subjects received twice-daily 25 mg oral doses of OM tablets. On Day 10, subjects received an 850 mg oral dose of metformin and a single 25 mg tablet of OM. Blood and urine samples were collected up to 36 h post-dose following administration of metformin on Days 1 and 10 to characterize concentrations of metformin in plasma and urine. RESULTS: The ratios of the geometric least square means of metformin coadministered with OM compared to metformin alone were 98.7%, 99.3%, and 110.2% for AUCinf, AUClast, and Cmax, respectively. The mean renal clearance of metformin was similar following metformin administered alone (34.2 L/h) compared to metformin coadministered with OM (32.9 L/h). All adverse events were mild in severity and resolved prior to the end of the study. No serious adverse events or treatment-emergent adverse events led to discontinuation from the study. CONCLUSIONS: There was no clinically relevant effect of OM on the pharmacokinetics of metformin in healthy subjects.


Assuntos
Metformina/farmacocinética , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Ureia/análogos & derivados , Administração Oral , Adulto , Área Sob a Curva , Diarreia/etiologia , Interações Medicamentosas/fisiologia , Feminino , Meia-Vida , Voluntários Saudáveis , Humanos , Análise dos Mínimos Quadrados , Masculino , Metformina/administração & dosagem , Metformina/efeitos adversos , Metformina/química , Pessoa de Meia-Idade , Curva ROC , Especificidade por Substrato , Comprimidos/química , Ureia/administração & dosagem , Ureia/efeitos adversos , Ureia/química
7.
Eur J Med Chem ; 222: 113579, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34098465

RESUMO

Genetic models validated Inhibitor of nuclear factor (NF) kappa B kinase beta (IKKß) as a therapeutic target for KRAS mutation associated pancreatic cancer. Phosphorylation of the activation loop serine residues (S177, S181) in IKKß is a key event that drives tumor necrosis factor (TNF) α induced NF-κB mediated gene expression. Here we conducted structure activity relationship (SAR) study to improve potency and oral bioavailability of a quinoxaline analog 13-197 that was previously reported as a NFκB inhibitor for pancreatic cancer therapy. The SAR led to the identification of a novel quinoxaline urea analog 84 that reduced the levels of p-IKKß in dose- and time-dependent studies. When compared to 13-197, analog 84 was ∼2.5-fold more potent in TNFα-induced NFκB inhibition and ∼4-fold more potent in inhibiting pancreatic cancer cell growth. Analog 84 exhibited ∼4.3-fold greater exposure (AUC0-∞) resulting in ∼5.7-fold increase in oral bioavailability (%F) when compared to 13-197. Importantly, oral administration of 84 by itself and in combination of gemcitabine reduced p-IKKß levels and inhibited pancreatic tumor growth in a xenograft model.


Assuntos
Antineoplásicos/farmacologia , Quinase I-kappa B/antagonistas & inibidores , Neoplasias Pancreáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Quinoxalinas/farmacologia , Ureia/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Quinase I-kappa B/metabolismo , Camundongos , Estrutura Molecular , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinoxalinas/síntese química , Quinoxalinas/química , Relação Estrutura-Atividade , Ureia/análogos & derivados , Ureia/química
8.
Chem Commun (Camb) ; 57(54): 6680-6683, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34132265

RESUMO

Carbon isotope labeling is a traceless technology, which allows tracking the fate of organic compounds either in the environment or in living organisms. This article reports on a general approach to label urea derivatives with all carbon isotopes, including 14C and 11C, based on a Staudinger aza-Wittig sequence. It provides access to all aliphatic/aromatic urea combinations.


Assuntos
Dióxido de Carbono/química , Radioisótopos de Carbono/química , Marcação por Isótopo/métodos , Ureia/química
9.
Int J Biol Macromol ; 184: 538-550, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34175336

RESUMO

In this study, two kinds of form-stable multifunctional materials with thermal and electrical response (FPCMs: DP-E7U3-CNT, DP-E7T3-CNT) are composed of wood-based honeycomb-like celluloses micro-framework (DP), carbon nanotubes (CNT), erythritol-urea (E7U3) or erythritol-thiourea (E7T3). In FPCMs, DP acts as a skeleton structure to seal E7U3 and E7T3 and provide more pathways for heat conduction. The CNT acts as an extended surface to further improve thermal conductivity. FE-SEM showed that the honeycomb-like pore structure of DP was completely filled with E7U3, E7T3 and CNT. FTIR and XRD analysis show that there is only a combination of physical interactions between the components of FPCMs. DSC curves and thermal conductivity analysis results show that DP-E7U3-1.5CNT and DP-E7T3-1.5CNT with the mass fraction of carbon nanotubes (1.5 wt%) have the highest latent heat values (230.3 J/g, 272.2 J/g) and thermal conductivity (0.9832 W/(m·K), 0.9363 W/(m·K)). Both DP-E7U3-1.5CNT and DP-E7T3-1.5CNT exhibit high latent heat retention and thermal stability after 100 heating-cooling cycles. In addition, DP-E7U3-1.5CNT and DP-E7T3-1.5CNT show excellent performance in light-heat energy conversion-storage, actual latent heat storage and release, thermal and electrical response performance, which make it has great potential to be multifunctional materials with thermal storage sand electrical response.


Assuntos
Celulose/química , Eritritol/química , Tioureia/química , Ureia/química , Condutividade Elétrica , Desenho de Equipamento , Teste de Materiais , Estrutura Molecular , Nanotubos de Carbono/química , Transição de Fase , Condutividade Térmica , Madeira/química
10.
Int J Biol Macromol ; 182: 1893-1905, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34081953

RESUMO

In this work, a number of glucose unites in polymeric structure of cellulose was converted to 2,4-dihydroxy-3-(1-hydroxy-2-oxoethoxy)butanal (cellulose containing di aldehyde units (CCDAUs)) by oxidation with sodium periodate, followed by condensation with acetone to produce 5,7-dihydroxy-6-((1-hydroxy-4-oxopent-2-en-1-yl)oxy)hept-3-en-2-one unites (cellulose containing di ene units (CCDEUs)). This modified cellulose was characterized by different methods and applied as a copolymer and grafting agent to synthesize an eco-friendly (CCDEUs-g-poly(AA)/urea) superabsorbent with slow-release urea fertilizer. The created double bonds in C2 and C3 positions of ß-d-glucose units increased the linkage between cellulose and acrylic acid, leading to the formation of a strong network for slow-release urea fertilizer. Also, this modification created an expanded network for storage a high amount of water by increasing the cellulose flexibility. The reaction conditions for modification and synthesis of the superabsorbent, the oxidation degree value of glucose units, kinetics models, the effect of different saline solutions, various pH and reswelling time on the water absorbency, water retention capacity, reusability, biodegradability, and slow-release property were investigated. Also, the effect of synthesized CCDEUs-g-poly(AA)/urea on plant growth was tested and excellent results were obtained.


Assuntos
Celulose/química , Fertilizantes/análise , Ureia/análise , Acrilamidas/química , Acrilatos/química , Adsorção , Sulfato de Amônio/química , Difusão , Elementos Químicos , Fabaceae/crescimento & desenvolvimento , Concentração de Íons de Hidrogênio , Cinética , Oxirredução , Reologia , Sais/química , Solo/química , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Termogravimetria , Ureia/síntese química , Ureia/química , Água/química
11.
World J Microbiol Biotechnol ; 37(6): 98, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33969436

RESUMO

This work was mainly about the understanding of how urea and ammonium affect growth, glucose consumption and ethanol production of S. cerevisiae, in particular regarding the basic physiology of cell. The basic physiology of cell included intracellular pH, ATP, NADH and enzyme activity. Results showed that fermentation time was reduced by 19% when using urea compared with ammonium. The maximal ethanol production rate using urea was 1.14 g/L/h, increasing 30% comparing with the medium prepared with ammonium. Moreover, urea could decrease the synthesis of glycerol from glucose by 26% comparing with ammonium. The by-product of acetic acid yields decreased from 40 mmol/mol of glucose (with urea) to 24 mmol/mol of glucose (with ammonium). At the end of ethanol fermentation, cell number and pH were greater with urea than ammonium. Comparing with urea, ammonium decreased the intracellular pH by 14% (from 7.1 to 6.1). Urease converting urea into ammonia resulted in a more than 50% lower of ATP when comparing with ammonium. The values of NADH/DCW were 0.21 mg/g and 0.14 mg/g respectively with urea and ammonium, suggesting a 33% lower NADH. The enzyme activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was 0.0225 and 0.0275 U/mg protein respectively with urea and ammonium, which was consistent with the yields of glycerol.


Assuntos
Compostos de Amônio/química , Etanol/química , Saccharomyces cerevisiae/fisiologia , Ureia/química , Trifosfato de Adenosina/metabolismo , Fermentação , Proteínas Fúngicas/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Glicerol/química , Concentração de Íons de Hidrogênio , NAD/metabolismo , Saccharomyces cerevisiae/metabolismo
12.
Bioorg Med Chem Lett ; 41: 128007, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33798699

RESUMO

NAD+ is a crucial cellular factor that plays multifaceted roles in wide ranging biological processes. Low levels of NAD+ have been linked to numerous diseases including metabolic disorders, cardiovascular disease, neurodegeneration, and muscle wasting disorders. A novel strategy to boost NAD+ is to activate nicotinamide phosphoribosyltransferase (NAMPT), the putative rate-limiting step in the NAD+ salvage pathway. We previously showed that NAMPT activators increase NAD+ levels in vitro and in vivo. Herein we describe the optimization of our NAMPT activator prototype (SBI-0797812) leading to the identification of 1-(4-((4-chlorophenyl)sulfonyl)phenyl)-3-(oxazol-5-ylmethyl)urea (34) that showed far more potent NAMPT activation and improved oral bioavailability.


Assuntos
Citocinas/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Ureia/farmacologia , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Ureia/análogos & derivados , Ureia/química
13.
Chem Commun (Camb) ; 57(43): 5330-5333, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-33928959

RESUMO

The role of urea as a kinetic promoter for the growth of CO2 hydrates is revealed for the first time using molecular dynamics simulations. Analysis of simulation trajectories shows that urea plays two important roles in the growth process: increasing mass transport of CO2 and catalyzing cage formation at the solid-liquid interface.


Assuntos
Dióxido de Carbono/química , Simulação de Dinâmica Molecular , Ureia/química , Tamanho da Partícula , Água/química
14.
Molecules ; 26(5)2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33800017

RESUMO

Metal-organic frameworks (MOFs) have become one of the versatile solid materials used for a wide range of applications, such as gas storage, gas separation, proton conductivity, sensors and catalysis. Among these fields, one of the more well-studied areas is the use of MOFs as heterogeneous catalysts for a broad range of organic reactions. In the present review, the employment of MOFs as solid catalysts for the Henry reaction is discussed, and the available literature data from the last decade are grouped. The review is organized with a brief introduction of the importance of Henry reactions and structural properties of MOFs that are suitable for catalysis. The second part of the review discusses the use of MOFs as solid catalysts for the Henry reaction involving metal nodes as active sites, while the third section provides data utilizing basic sites (primary amine, secondary amine, amides and urea-donating sites). While commenting on the catalytic results in these two sections, the advantage of MOFs over other solid catalysts is compared in terms of activity by providing turnover number (TON) values and the structural stability of MOFs during the course of the reaction. The final section provides our views on further directions in this field.


Assuntos
Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/metabolismo , Amidas/química , Aminas/química , Catálise , Domínio Catalítico , Cobre/química , Ureia/química
15.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809178

RESUMO

The genome of the human intracellular pathogen Mycobacterium tuberculosis encodes an unusually large number of epoxide hydrolases, which are thought to be involved in lipid metabolism and detoxification reactions needed to endure the hostile environment of host macrophages. These enzymes therefore represent suitable targets for compounds such as urea derivatives, which are known inhibitors of soluble epoxide hydrolases. In this work, we studied in vitro the effect of the thiourea drug isoxyl on six epoxide hydrolases of M. tuberculosis using a fatty acid substrate. We show that one of the proteins inhibited by isoxyl is EphD, an enzyme involved in the metabolism of mycolic acids, key components of the mycobacterial cell wall. By analyzing mycolic acid profiles, we demonstrate the inhibition of EphD epoxide hydrolase activity by isoxyl and two other urea-based inhibitors, thiacetazone and AU1235, inside the mycobacterial cell.


Assuntos
Epóxido Hidrolases/antagonistas & inibidores , Tioureia/farmacologia , Tuberculose/tratamento farmacológico , Ureia/farmacologia , Adamantano/análogos & derivados , Adamantano/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Compostos de Fenilureia/farmacologia , Tioacetazona/farmacologia , Tioureia/análogos & derivados , Tuberculose/enzimologia , Tuberculose/microbiologia , Ureia/química
16.
J Sci Food Agric ; 101(13): 5541-5549, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33709464

RESUMO

BACKGROUND: Meeting the energy and nitrogen (N) requirements of high-performing ruminants at the same time as avoiding digestive disturbances (i.e. rumen acidosis) is a key priority in ruminant nutrition. The present study evaluated the effect of a cereal ammoniation treatment, in which barley grains are combined with urea and enzymes that catalyze the conversion of urea to ammonia to optimize rumen function. Twelve rumen cannulated sheep were randomly divided into two groups and fed a diet containing 60% of ammoniated barley (AMM) or untreated barley supplemented with urea (CTL) to investigate the impact on rumen fermentation and feed utilization. RESULTS: AMM had higher total N content and effective rumen degradable N than untreated barely. AMM sheep had a consistently higher rumen pH throughout the day (6.31 versus 6.03) and tended to have a lower post-prandial ammonia peak and higher acetate molar proportion (+5.1%) than CTL sheep. The rumen environment in AMM sheep favored the colonization and utilization of agro-industrial by-products (i.e. orange pulp) by the rumen microbes leading to a higher feed degradability. AMM sheep also had higher total tract apparent N digestibility (+21.7%) and urinary excretion of purine derivatives (+34%), suggesting a higher N uptake and microbial protein synthesis than CTL sheep. CONCLUSION: The inclusion of AMM in the diet of ruminants represents a valid strategy for maintaining rumen pH within a physiological range and improving N utilization by the rumen microbes, which could have positive effects on the health and productivity of animals in intensive production systems. These findings warrant further studies under conventional farm conditions. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Amônia/química , Ração Animal/análise , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Manipulação de Alimentos/métodos , Hordeum/química , Rúmen/metabolismo , Ovinos/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Proteínas de Bactérias/genética , Dieta/veterinária , Digestão , Microbioma Gastrointestinal , Hordeum/metabolismo , Concentração de Íons de Hidrogênio , Rúmen/química , Rúmen/microbiologia , Ureia/química
17.
J Enzyme Inhib Med Chem ; 36(1): 764-775, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33733986

RESUMO

Antibiotics resistance is becoming increasingly common, involving almost all antibiotics on the market. Diseases caused by drug resistant bacteria, such as MRSA, have high mortality and negatively affect public health. The development of new drugs would be an effective means of solving this problem. Modifications based on bioactive natural products could greatly shorten drug development time and improve success rate. Pleuromutilin, a natural product from the basidiomycete bacterial species, is a promising antibiotic candidate. In this study, a series of novel pleuromutilin derivatives possessing piperazinyl urea linkage were efficiently synthesised, and their antibacterial activities and bactericidal properties were evaluated via MIC, MBC and Time-kill kinetics assays. The results showed that all compounds exhibited potent activities against tested strains, especially MRSA strains with MIC values as low as 0.125 µg/mL; 8 times lower than that of marketed antibiotic Tiamulin. Docking studies indicate substituted piperazinyl urea derivatives could provide hydrogen bonds and initiate π-π stacking between molecules and surrounding residues.


Assuntos
Antibacterianos/farmacologia , Diterpenos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Simulação de Acoplamento Molecular , Compostos Policíclicos/farmacologia , Ureia/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Diterpenos/síntese química , Diterpenos/química , Células HEK293 , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Policíclicos/síntese química , Compostos Policíclicos/química , Ureia/análogos & derivados , Ureia/química
18.
Methods Mol Biol ; 2283: 15-20, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33765304

RESUMO

The concept of the urea breath test (UBT), as a method for H. pylori detection, is based on the ability of the H. pylori urease enzyme to break down an isotope-labelled urea solution ingested by the patient into carbon dioxide (CO2) and ammonia. This chapter summarizes the current use of the UBT and the utility of the "UBT and Treat" strategy compared to other strategies for the management of H. pylori infection . Different UBT methods are described as well as factors affecting the accuracy of the test.


Assuntos
Infecções por Helicobacter/diagnóstico , Helicobacter pylori/enzimologia , Ureia/administração & dosagem , Urease/metabolismo , Amônia/química , Proteínas de Bactérias/metabolismo , Testes Respiratórios , Dióxido de Carbono/química , Feminino , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Sensibilidade e Especificidade , Ureia/química
19.
Angew Chem Int Ed Engl ; 60(19): 10833-10841, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33624345

RESUMO

The m-pyridine urea (mPU) oligomer was constructed by using the intramolecular hydrogen bond formed by the pyridine nitrogen atom and the NH of urea and the intermolecular hydrogen bond of the terminal carbonyl group and the NH of urea. Due to the synergistic effect of hydrogen bonds, mPU oligomer folds and exhibits strong self-assembly behaviour. Affected by folding, mPU oligomer generates a twisted plane, and one of its important features is that the carbonyl group of the urea group orientates outwards from the twisted plane, while the NHs tend to direct inward. This feature is beneficial to NH attraction for electron-rich species. Among them, the trimer self-assembles into helical nanotubes, and can efficiently transport chloride ions. This study provides a novel and efficient strategy for constructing self-assembled biomimetic materials for electron-rich species transmission.


Assuntos
Materiais Biomiméticos/química , Canais de Cloreto/química , Piridinas/química , Ureia/química , Tamanho da Partícula , Propriedades de Superfície
20.
J Biochem ; 169(5): 565-573, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-33630058

RESUMO

Titanium is the only metal to which osteoblasts can adhere and on which they can grow and form bone tissue in vivo, resulting in a strong bond between the implant and living bone. This discovery provides the basis for the universal medical application of Ti. However, the biochemical mechanism of bond formation is still unknown. We aimed to elucidate the mechanism of bond formation between collagen, which constitutes the main organic component of bone, and TiO2, of which the entire surface of pure Ti is composed. We analysed the binding between the soluble collagen and TiO2 by chromatography with a column packed with Ti beads of 45 µm, and we explored the association between collagen fibrils and TiO2 (anatase) powders of 0.2 µm. We ran the column of chromatography under various elution conditions. We demonstrated that there is a unique binding affinity between Ti and collagen. This binding capacity was not changed even in the presence of the dissociative solvent 2M urea, but it decreased after heat denaturation of collagen, suggesting the contribution of the triple-helical structure. We propose a possible role of periodically occurring polar amino acids and the collagen molecules in the binding with TiO2.


Assuntos
Colágeno/química , Titânio/química , Ureia/química , Cromatografia Líquida , Colágeno/isolamento & purificação , Desnaturação Proteica
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