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1.
Sci Rep ; 13(1): 13728, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37608052

RESUMO

Oxidative desulfurization (ODS) is considered to be one of the most promising desulfurization processes as it is energy-efficient and requires mild operating conditions. In this study, a novel green synthesized Al- based metal-organic framework with high surface area has been synthesized hydrothermally using waste polyethylene terephthalate bottles (PET) as a source of terephthalic acid as an organic linker. The prepared Al based MOF have been characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM) and transmission electron microscopy (TEM). The catalytic activity of the prepared Al-MOF was evaluated in the oxidative desulfurization (ODS) of both modeled and real crude oil samples. The different operating parameters (temperature, time, catalyst dose, oxidant loading and sonication) on the ODS performance have been optimized. The optimal conditions for maximum removal of thiophene from modeled oil samples were found to be 30 min, 0.5 g of catalyst and 1:3 oil to oxidant ratio. Under the optimized conditions, sulfur removal in real oil samples obtained from Alexandria petroleum company was 90%. The results revealed that, the presented approach is credited to cost-effectiveness, environmental benignity, and ease of preparation, predicting great prospects for desulfurization of fuel oils on a commercial level.

2.
BMC Public Health ; 23(1): 949, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-37231362

RESUMO

BACKGROUND: The global prevalence of abnormal glycemic level comprising diabetes mellitus (DM) and pre-diabetes (PDM) is rapidly increasing with special concern for the entity silent or undiagnosed diabetes; those unaware of their condition. Identification of people at risk became much easier with the use of risk charts than the traditional methods. The current study aimed to conduct a community-based screening for T2DM to estimate the prevalence of undiagnosed DM and to assess the AUSDRISK Arabic version as a predictive tool in an Egyptian context. METHODS: A cross-sectional study was conducted among 719 Adults aging 18 years or more and not known to be diabetics through a population-based household survey. Each participant was interviewed to fill demographic and medical data as well as the AUSDRISK Arabic version risk score and undergo testing for fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT). RESULTS: The prevalence of DM and PDM were 5% and 21.7% respectively. The multivariate analysis revealed that age, being physically inactive, history of previous abnormal glycemic level and waist circumference were the predictors for having abnormal glycemic level among the studied participants. At cut off points ≥ 13 and ≥ 9, the AUSDRISK respectively discriminated DM [sensitivity (86.11%), specificity (73.35%), and area under the curve (AUC): 0.887, 95% CI: 0.824-0.950] and abnormal glycemic level [sensitivity (80.73%), specificity (58.06%), and AUC: 0.767, 95% CI: 0.727-0.807], p < 0.001. CONCLUSIONS: Overt DM just occupies the top of an iceberg, its unseen big population have undiagnosed DM, PDM or been at risk of T2DM because of sustained exposure to the influential risk factors. The AUSDRISK Arabic version was proved to be sensitive and specific tool to be used among Egyptians as a screening tool for the detection of DM or abnormal glycemic level. A prominent association has been demonstrated between AUSDRISK Arabic version score and the diabetic status.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Estado Pré-Diabético , Humanos , Adulto , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Prevalência , Estudos Transversais , Egito/epidemiologia , Glicemia/análise , Fatores de Risco , Diabetes Mellitus/epidemiologia
3.
Can J Nurs Res ; 55(2): 216-229, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35876326

RESUMO

BACKGROUND: Caring for older adults is among the most challenging issue of public health and social care systems in modern societies. By enhancing the nursing curriculum, nursing students will be qualified to provide gerontology care, and they will be acknowledging and working to eliminate ageism from the health care system. PURPOSE: This study explores nurses' and nursing students' knowledge and attitudes in caring for older adults and addresses the factors contributing to nurses' perspectives. It also examines the nursing curriculum's contributions to nurses' knowledge and attitudes and provides suggestions aimed at reconfiguring the nursing curriculum for comprehensive gerontology nursing care. METHODS: A mixed-method research design was utilized, and quantitative and qualitative data were collected from 90 nurses and nursing students through an online questionnaire. Data were analyzed via SPSS and NVivo 12 software programs. RESULTS: The results revealed that most nurses possess neutral attitudes toward caring for older patients, and their knowledge ranged from average to above-average levels. Statistical analysis revealed no statistically significant difference between gender and nurses' attitudes or between gender and knowledge. Similarly, there was no statistically significant difference between work status and nurses' attitudes. Results showed a statistically significant positive correlation between nurses' attitudes and knowledge level. This study demonstrated the positive impact of the Canadian nursing curriculum on nurses' knowledge and attitudes. CONCLUSION: The current study recommends providing gerontology nursing courses as a mandatory separate course in nursing education to enhance nursing students' knowledge and skills for high-quality gerontology nursing care.


Assuntos
Enfermeiras e Enfermeiros , Estudantes de Enfermagem , Humanos , Idoso , Competência Clínica , Canadá , Currículo , Inquéritos e Questionários , Atitude do Pessoal de Saúde
4.
BMC Res Notes ; 15(1): 303, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138452

RESUMO

OBJECTIVE: The current study aimed to translate the Australian Type 2 Diabetes Risk Assessment tool (AUSDRISK) into the Arabic language and evaluate the reliability and validity of the resultant Arabic version among Egyptians. The AUSDRISK was translated into Arabic language using the World Health Organization (WHO) forward and backward translation protocol. Using the WHO cluster sampling, a sample of 18+ years 719 Egyptians was randomly selected through a population-based household survey. Each participant was interviewed to fill the AUSDRISK Arabic version risk score and undergo confirmatory testing for fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT). Test-retest reliability and convergent validity were computed. RESULTS: Most of the study participants were physically active (60.5%) and females (69.3%). The Arabic version of the AUSDRISK reflected statistically significant perfect positive correlation (r = 1 and p < 0.01) for test re-test reliability as well as a significant moderate positive correlation with each of FPG (r = 0.48, p < 0.01) and OGTT (r = 0.52, p < 0.01) for the criterion-related (convergent) validity. The recalibrated noninvasive AUSDRISK Arabic version proved to be a simple, reliable, and valid predictive tool, and thereof, its employment for opportunistic mass public screening is strongly recommended. This can reduce diabetes mellitus Type 2disease burden and health expenditure.


Assuntos
Diabetes Mellitus Tipo 2 , Idioma , Austrália , Glicemia , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Psicometria , Reprodutibilidade dos Testes , Medição de Risco , Inquéritos e Questionários
6.
Acta Chim Slov ; 68(2): 304-312, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34738118

RESUMO

Natural gas is a mixture that is widely used in the industries. Knowledge of its thermodynamic properties is essential for evaluating the process and equipment performance. This paper quantifies the energy that can be extracted from natural gas using a turbo expander. Natural gases of wide-ranging compositions collected from 6 different gas fields in Egypt were investigated based on energy and exergy analysis. The study was conducted using MATLAB. Numerous simulation runs were made by taking various typical feed compositions classified as lean and rich. The effects of increasing the amount of C1, C5 in the feed stream on the efficiency of energy utilization are presented. A validation analysis was performed. The results show similar trends and good agreements. It was concluded from the results that when the concentration of methane in the gas mixture increase, the exergetic efficiency decreases. The results also show that the values of thermodynamic properties depend on the relative amount of heavy components in the feed stream.

7.
Bioorg Chem ; 105: 104366, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33212312

RESUMO

In recent years, cell cycle and checkpoint pathways regulation are offering new therapeutic approaches against cancer. Isatin, is a well exploited scaffold in the anticancer domain. Accordingly, the current work describes the design and synthesis of two series of (Z)-3-substituted-2-(((E/Z)-5-substituted-2-oxo-1-substituted-indolin-3-ylidene)hydrazinylidene)-thiazolidin-4-ones, 4(a-s) and (E/Z)-1-substituted-3-(((Z)-3-substituted-4-methylthiazol-2(3H)-ylidene)hydrazineylidene)-5-substituted-indolin-2-ones, 5(a-s). The structures of the synthesized molecules were confirmed by spectral and elemental methods of analyses. Pure diastereomers were further identified with 1H-1H-NOESY and confirmed with X-ray crystallography. The target compounds were tested in vitro for their cytotoxicity against three human epithelial cell lines, liver (HepG2), breast (MCF-7), and colon (HT-29) in addition to the diploid human normal cells (WI-38) compared to doxorubicin as a reference drug. Variable cytotoxic effects (IC50 3.29-100 µmol) were reported on the three cancer cell lines with pronounced selectivity compared to the normal one WI-38. The potency of the most active compounds, 4o, 4s, 5e, 5f, 5l, 5m and 5o (IC50 3.29-9.92 µmol), in both series associated with the (Z) configurations of N = thiazolidin/ene or one, however, the configuration of the N = isatin moiety seemed to be of no importance to the activity. The tested compounds were grouped for their possible mechanism of action into 4 categories. Compound 4o with no apparent effect on all genes examined. Compounds 4s and 5o affected all genes investigated and seem to have multiple cellular targets; induced the expression of p53 and caspases, and downregulated that of CDK1. Compounds 5l and 5m directly elevated the expression of initiator and effector caspases without going through p53 pathway. Finally, compounds 5e and 5f elevated the expression of p53 and inhibited CDK1. Compounds 4s, 5e, 5f, 5l, 5m, and 5o caused a significant elevation in the activity of cleaved caspase 3 as well. Docking studies on CDK1 revealed that the active molecules bind to the tested enzyme by the same manner of the co-crystallized ligands and the isatin-thiazoldinone/ene scaffold is essential for binding of these molecules.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Isatina/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isatina/síntese química , Isatina/química , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
8.
Environ Sci Pollut Res Int ; 26(32): 32804-32814, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31502052

RESUMO

Biodiesel appears to be a possible substitute for non-renewable fossil fuels; however, its production requires the presence of a catalyst to accelerate the reaction. Serving the purpose of finding effective, cheap and environmentally safe, heterogeneous catalysts, this research used the fig leaves in three different forms, calcined, activated by KOH, and activated by both K2CO3 and CaCO3. Their efficiency in biodiesel synthesis, from spent cooking oil, was examined and compared with that of activated carbon which has been previously investigated. The properties of different catalyst forms were specified using X-ray diffraction, scanning electron microscope and Fourier transform infrared spectroscopy. Operating parameters studied for the three catalysts were reaction time (from 30 to 180 min), alcohol-to-oil molar ratio (from 4:1 to 10:1), catalyst loading (from 0.5 to 5% by wt.), and stirring speed (from 100 to 400 rpm). The increase in reaction time, molar ratio, and catalyst loading proved to have a favorable effect on % conversion to biodiesel but to a certain degree; increasing the stirring speed augmented the conversion. At optimum conditions (2 h of heating, 6:1 alcohol-to-oil molar ratio, 1% by wt. catalyst loading, and 400 rpm stirring), fig leaves activated by KOH provided the highest conversion to biodiesel (92.73%). The measured properties of the produced biodiesel (density, viscosity, flash point, cloud point, and pour point) yielded encouraging results. Graphical Abstract.


Assuntos
Biocombustíveis/análise , Culinária , Ficus , Catálise , Esterificação , Folhas de Planta/química , Óleos de Plantas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
9.
Int Health ; 10(6): 502-516, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30053060

RESUMO

Background: Written personalized asthma action plans are recommended as part of patient education and self-management. Objectives: To enable asthmatic adults to proactively self-manage bronchial asthma and sustain asthma quiescent status through utilization of the Asthma Action Plan (AAP), and to establish a feasible asthmatic/care taker-health care provider communication. Design: Randomized controlled trial with cluster sampling by pulmonologists. Setting and participants: The study comprised 320 chronic asthmatic patients attending the chest department at the main health insurance hospital in Alexandria that were randomly allocated as the intervention group (AAIG; n=160) that received standard care and intervention by the AAP and a control group (AACG; n=160) that received the routine standard of care. Data were collected through an interviewing questionnaire. The study continued over a 6-month period and passed into three phase stations. During the preparatory phase the health care provider managed to explain, fill and simplify the use of the Arabic version of the AAP, to explain the correct utilization of the weekly follow-up form and to emphasize the weekly communication/visit with the health care provider (HCP) to update their weekly follow-up records. Follow-up was done on the 90th and 180th days from the launch of the study, respectively. The study asthmatics were subjected to history-taking of their asthma symptoms, signs and triggers, and a review of their medical/peak expiratory flow records, as well as his/her daily activity and exercise. Results: The AAIG experienced superiority of the average of the green zone days ('doing well') with significantly more episodes of early asthma flare-up self-management concomitant with prominent fewer emergency department visits, hospitalization, admission at the ICU, private health facility, and days of sickness leaves and absenteeism. A preponderance of the high and medium adherence levels to asthma medications, avoidance of asthma triggers and smoking was achieved by the AAIG. Conclusions: AAP was the basis for effective patient-health care provider communication and patient real time asthma flare-up self-management to achieve and sustain better asthma control in asthmatic adults.


Assuntos
Asma/terapia , Educação de Pacientes como Assunto/métodos , Autogestão/métodos , Atividades Cotidianas , Adulto , Fatores Etários , Idoso , Doença Crônica , Serviço Hospitalar de Emergência , Feminino , Comportamentos Relacionados com a Saúde , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Autocuidado , Fatores Sexuais , Fatores Socioeconômicos , Adulto Jovem
10.
J Med Chem ; 61(3): 1218-1230, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29328649

RESUMO

Lead structure discovery mainly focuses on the identification of noncovalently binding ligands. Covalent linkage, however, is an essential binding mechanism for a multitude of successfully marketed drugs, although discovered by serendipity in most cases. We present a concept for the design of fragments covalently binding to proteases. Covalent linkage enables fragment binding unrelated to affinity to shallow protein binding sites and at the same time allows differentiated targeted hit verification and binding location verification through mass spectrometry. We describe a systematic and rational computational approach for the identification of covalently binding fragments from compound collections inhibiting enteroviral 3C protease, a target with high therapeutic potential. By implementing reactive groups potentially forming covalent bonds as a chemical feature in our 3D pharmacophore methodology, covalent binders were discovered by high-throughput virtual screening. We present careful experimental validation of the virtual hits using enzymatic assays and mass spectrometry unraveling a novel, previously unknown irreversible inhibition of the 3C protease by phenylthiomethyl ketone-based fragments. Subsequent synthetic optimization through fragment growing and reactivity analysis against catalytic and noncatalytic cysteines revealed specific irreversible 3C protease inhibition.


Assuntos
Cisteína Endopeptidases/metabolismo , Inibidores de Cisteína Proteinase/química , Inibidores de Cisteína Proteinase/farmacologia , Enterovirus/enzimologia , Cetonas/química , Cetonas/farmacologia , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/metabolismo , Proteases Virais 3C , Domínio Catalítico , Cisteína Endopeptidases/química , Inibidores de Cisteína Proteinase/metabolismo , Desenho de Fármacos , Ensaios de Triagem em Larga Escala , Cetonas/metabolismo , Modelos Moleculares , Relação Estrutura-Atividade , Especificidade por Substrato , Proteínas Virais/química
11.
Ecotoxicol Environ Saf ; 145: 57-68, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28708982

RESUMO

Polyethyleneterephthalate (PET) is an important component of post-consumer plastic waste. This study focuses on the potential of utilizing "waste-treats-waste" by synthesis of graphene using PET bottle waste as a source material. The synthesized graphene is characterized by SEM, TEM, BET, Raman, TGA, and FT-IR. The adsorption of methylene blue (MB) and acid blue 25 (AB25) by graphene is studied and parameters such as contact time, adsorbent dosage were optimized. The Response Surface Methodology (RSM) is applied to investigate the effect of three variables (dye concentration, time and temperature) and their interaction on the removal efficiency. Adsorption kinetics and isotherm are followed a pseudo-second-order model and Langmuir and Freundlich isotherm models, respectively. Thermodynamic parameters demonstrated that adsorption of dye is spontaneous and endothermic in nature. The plastic waste can be used after transformation into valuable carbon-based nanomaterials for use in the adsorption of organic contaminants from aqueous solution.


Assuntos
Corantes/análise , Grafite/química , Plásticos/química , Polietilenotereftalatos/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Química Verde , Cinética , Reciclagem , Temperatura , Águas Residuárias/química
12.
J Air Waste Manag Assoc ; 67(3): 358-370, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27700617

RESUMO

Nowadays our planet suffers from an accumulation of plastic products that have the potential to cause great harm to the environment in the form of air, water, and land pollution. Plastic water bottles have become a great problem in the environment because of the large numbers consumed throughout the world. Certain types of plastic bottles can be recycled but most of them are not. This paper describes an economical solvent-free process that converts polyethylene terephthalate (PET) bottles waste into carbon nanostructure materials via thermal dissociation in a closed system under autogenic pressure together with additives and/or catalyst, which can act as cluster nuclei for carbon nanostructure materials such as fullerenes and carbon nanotubes. This research succeeded in producing and controlling the microstructure of various forms of carbon nanoparticles from the PET waste by optimizing the preparation parameters in terms of time, additives, and amounts of catalyst. IMPLICATIONS: Plastic water bottles are becoming a growing segment of the municipal solid waste stream in the world; some are recycled but many are left in landfill sites. Recycling PET bottles waste can positively impact the environment in several ways: for instance, reduced waste, resource conservation, energy conservation, reduced greenhouse gas emissions, and decreasing the amount of pollution in air and water sources. The main novelty of the present work is based on the acquisition of high-value carbon-based nanomaterials from PET waste by a simple solvent-free chemical technique. Thus, the prepared materials are considered to be promising, cheap, eco-friendly materials that may find use in different applications.


Assuntos
Nanotubos de Carbono/química , Polietilenotereftalatos/química , Gerenciamento de Resíduos/métodos , Meio Ambiente , Plásticos , Reciclagem , Resíduos Sólidos , Água
13.
Eur J Med Chem ; 93: 481-91, 2015 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-25732770

RESUMO

A group of N-malonyl-1,2-dihydroisoquinoline derivatives were synthesized and investigated as brain specific and shelf-stable MAO inhibitors. N-malonyl-1,2-dihydroisoquinoline redox carrier system was linked through amidic bond to 4-chloro and 4-nitrobenzylidenehydrazines (9a-b), as monoamine oxidase inhibitors (MAOIs), and ß-phenethylamine (14), as a model drug, to afford a novel group of N-malonyl-1,2-dihydroisoquinoline chemical delivery systems (DHIQCDSs) (13a-b and 18). These systems are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydroisoquinoline. The synthesized DHIQCDS (18) was subjected to various chemical and biological investigations to evaluate its stability and prove its ability to cross the blood brain barrier and "lock-in" the brain. The in vitro chemical and enzymatic oxidation studies showed reasonable stability and adequate rate of conversion of DHIQCDS (18) to its corresponding quaternary metabolites. In vivo distribution study in rats revealed preferential concentration of the active moiety in the brain. Moreover, compounds (9a-b, 12a-b and 17) were screened for their in vitro MAO inhibitory activity compared to clorgyline as a reference compound. The inhibition profile was found to be competitive for both MAO-A and MAO-B isozymes with more selectivity toward MAO-A. Molecular docking study of compounds (9a-b, 12a-b and 17) and the suggested metabolites was carried out on both MAO-A and MAO-B isozymes. Observation of the docked poses revealed many interactions with many residues previously reported to have an effect on the inhibition of MAO enzyme.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Isoquinolinas/síntese química , Isoquinolinas/farmacologia , Malonatos/síntese química , Malonatos/farmacologia , Simulação de Acoplamento Molecular , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/farmacologia , Animais , Domínio Catalítico , Bovinos , Técnicas de Química Sintética , Estabilidade de Medicamentos , Feminino , Isoquinolinas/química , Isoquinolinas/metabolismo , Malonatos/química , Malonatos/metabolismo , Monoaminoxidase/química , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/metabolismo , Especificidade de Órgãos , Coelhos , Ratos
14.
Eur J Med Chem ; 54: 907-13, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22703846

RESUMO

A group of nitric oxide (NO) donating chalcone derivatives was prepared by binding amino chalcones with different NO-donating moieties including; nitrate esters, oximes and furoxans. Screening of the anticancer activity of the target compounds revealed that the selected NO-donating compounds exhibited from mild to strong cytotoxic activity. The NO/chalcone hybrids 3a and 3b exhibited remarkable activity against different types of cancer cell lines especially against the colon and melanoma cancer cell lines. The nitrate ester 3a exhibited moderate selectivity toward colon cancer subpanel with selectivity ratio of 5.87 at TGI level.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Chalcona/síntese química , Chalcona/farmacologia , Desenho de Fármacos , Óxido Nítrico/química , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Linhagem Celular Tumoral , Chalcona/efeitos adversos , Chalcona/química , Técnicas de Química Sintética , Humanos , Úlcera/induzido quimicamente
15.
Bioorg Med Chem ; 20(1): 195-206, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22137931

RESUMO

A group of novel nitric oxide (NO) donating chalcone derivatives was prepared by binding various amino chalcones with different NO donating moieties including; nitrate ester, oximes and furoxans. Most of the prepared compounds showed significant anti-inflammatory activity using carrageenan-induced rat paw edema method compared with indomethacin. The prepared compounds exhibited more protection than indomethacin in regard to gastric toxicity. Histopathological investigation confirmed the beneficial effects of the NO releasing compounds in reducing ulcer formation. The incorporation of the NO-donating group into the parent chalcone derivatives caused a moderate increase in the anti-inflammatory activity with a marked decrease in gastric ulcerations compared to their parent chalcone derivatives.


Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Chalcona/química , Edema/tratamento farmacológico , Doadores de Óxido Nítrico/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/uso terapêutico , Carragenina/toxicidade , Edema/induzido quimicamente , Edema/patologia , Trato Gastrointestinal/efeitos dos fármacos , Indometacina/farmacologia , Óxido Nítrico/metabolismo , Ratos
16.
Arch Pharm (Weinheim) ; 343(1): 54-60, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19899103

RESUMO

N-Malonyl-1,2-dihydroisoquinoline derivatives were synthesized and investigated as a novel carrier system for site-specific and sustained delivery of drugs to the brain. Such carriers are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydroisoquinoline. Reduction of the prepared isoquinolinium quaternary derivatives with sodium dithionite afforded a novel group of N-malonyl-1,2-dihydroisoquinoline chemical delivery systems (CDS). The synthesized N-malonyl-1,2-dihydroisoquinoline chemical delivery systems were subjected to various chemical and biological investigations to evaluate their ability to cross the blood-brain barrier (BBB), and to be oxidized biologically into their corresponding quaternary derivatives. The in-vitro oxidation studies showed that the designed N-malonyl-1,2-dihydroisoquinoline chemical delivery system could be oxidized into its corresponding quaternary derivatives at an adequate rate. The in-vivo distribution studies showed that these N-malonyl-1,2-dihydroisoquinoline chemical delivery systems were able to cross the blood-brain barrier at detectable concentrations.


Assuntos
Encéfalo/metabolismo , Portadores de Fármacos/química , Isoquinolinas/química , Malonatos/química , Animais , Barreira Hematoencefálica , Portadores de Fármacos/farmacocinética , Estabilidade de Medicamentos , Isoquinolinas/farmacocinética , Masculino , Malonatos/farmacocinética , Camundongos , Oxirredução , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
17.
Bioorg Med Chem ; 17(11): 3829-37, 2009 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-19419878

RESUMO

Some novel pyrazole-NO hybrid molecules 5a-e, 6, 8 and 10 were prepared through binding of the pyrazole-3-carboxylic acid derivatives with nitric oxide donor moiety like oxime or nitrate ester. The prepared compounds were evaluated for nitric oxide release, antibacterial and anti-inflammatory activities. The organic nitrate 10 exhibited the highest percentage of NO release using Griess diazotization method. Some of the prepared compounds exhibited remarkable antibacterial activity against Escherichia coli C-600, Pseudomonas aeruginosa, Bacillus subitilis and Staphylococcus aureus NCTC 6571 compared to ciprofloxacin. Most of the tested compounds showed significant anti-inflammatory activity compared to indomethacine using carrageenan induced paw edema method. In general, structural modification of compound 2 either to nitrate ester or oxime hybrids showed better anti-inflammatory with less ulcerogenic liability than their corresponding starting intermediates.


Assuntos
Ácidos Carboxílicos/química , Desenho de Fármacos , Óxido Nítrico/química , Pirazóis/química , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Bactérias/efeitos dos fármacos , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/farmacologia , Estrutura Molecular , Óxido Nítrico/metabolismo , Pirazóis/síntese química , Pirazóis/farmacologia , Ratos
18.
Bioorg Med Chem ; 17(10): 3665-70, 2009 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-19398345

RESUMO

The discovery of the inducible isoform of cyclooxygenase enzyme (COX-2) spurred the search for anti-inflammatory agents devoid of the undesirable effects associated with classical NSAIDs. New chlorzoxazone ester prodrugs (6-8) of some acidic NSAIDs (1-3) were designed, synthesized and evaluated as mutual prodrugs with the aim of improving the therapeutic potency and retard the adverse effects of gastrointestinal origin. The structure of the synthesized mutual ester prodrugs (6-8) were confirmed by IR, (1)H NMR, mass spectroscopy (MS) and their purity was ascertained by TLC and elemental analyses. In vitro chemical stability revealed that the synthesized ester prodrugs (6-8) are chemically stable in hydrochloric acid buffer pH 1.2 as a non-enzymatic simulated gastric fluid (SGF) and in phosphate buffer pH 7.4 as non-enzymatic simulated intestinal fluid (SIF). In 80% human plasma, the mutual prodrugs were found to be susceptible to enzymatic hydrolysis at relatively faster rate (t(1/2) approximately 37 and 34 min for prodrugs 6 and 7, respectively). Mutual ester prodrugs (6-8) were evaluated for their anti-inflammatory and muscle relaxation activities. Scanning electromicrographs of the stomach showed that the ester prodrugs induced very little irritancy in the gastric mucosa of rats after oral administration for 4days. In addition, docking of the mutual ester prodrugs (6-8) into COX-2 active site was conducted in order to predict the affinity and orientation of these prodrugs at the enzyme active site.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ácidos Carboxílicos/química , Clorzoxazona/análogos & derivados , Clorzoxazona/farmacologia , Pró-Fármacos/farmacologia , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Ácidos Carboxílicos/síntese química , Domínio Catalítico , Clorzoxazona/síntese química , Clorzoxazona/química , Simulação por Computador , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Desenho de Fármacos , Estabilidade de Medicamentos , Ésteres/síntese química , Ésteres/química , Ésteres/farmacologia , Masculino , Pró-Fármacos/síntese química , Pró-Fármacos/química , Ratos , Ratos Wistar , Relação Estrutura-Atividade
19.
Bioorg Med Chem ; 17(4): 1681-92, 2009 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-19147368

RESUMO

A group of 1-malonyl-1,4-dihydropyridine derivatives were synthesized as novel carrier systems for site-specific and sustained drug delivery to the brain. Such carriers are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydropyridine. These carrier systems were attached to a group of different aldehydes to afford novel quaternary pyridinium derivatives 9a-e, 11a-d, 13 and 18a-b. Reduction of the prepared quaternary pyridinium derivatives with sodium dithionite afforded a novel group of 1-malonyl-1,4-dihydropyridine chemical delivery systems (CDSs) 10a-e, 12a-d, 14 and 19a-b. The synthesized 1-malonyl-1,4-dihydropyridine CDSs were subjected to various chemical and biological investigations to evaluate their ability to cross the blood-brain barrier, and to be oxidized biologically into their corresponding quaternary derivatives. The in vitro oxidation studies showed that most of the 1-malonyl-1,4-dihydropyridine CDSs could be oxidized into their corresponding quaternary derivatives at an adequate rate. The in vivo studies showed that compounds 10c and 14 were able to cross the blood-brain barrier at detectable concentrations. Moreover, the pyridinium quaternary intermediates 9a, 9c, 13, 18a and their corresponding dihydro derivatives 10a, 10c, 14 and 19a were screened for their antidepressant activity using tail suspension behavioral despair test compared to imipramine as a reference at a dose level of 10mg/kg. The results indicated that compounds 13, 14 and 19a induced remarkable antidepressant activity comparable to imipramine. Compounds 10a, 10c and 18a exhibited good antidepressant activity, their activities nearly equal to 92.8%, 86.7% and 90.20% of the activity of imipramine, respectively. The other derivatives 9a and 9c exhibited moderate antidepressant activity compared with imipramine.


Assuntos
Encéfalo/metabolismo , Di-Hidropiridinas/química , Di-Hidropiridinas/farmacocinética , Portadores de Fármacos/química , Malonatos/química , Malonatos/farmacocinética , Animais , Antidepressivos/administração & dosagem , Antidepressivos/química , Antidepressivos/farmacocinética , Barreira Hematoencefálica , Di-Hidropiridinas/administração & dosagem , Portadores de Fármacos/farmacocinética , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Isoniazida/administração & dosagem , Isoniazida/química , Isoniazida/farmacocinética , Masculino , Camundongos , Oxirredução , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Distribuição Tecidual
20.
Eur J Med Chem ; 44(7): 3068-76, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18722034

RESUMO

A group of 3,5-diaryl-2-pyrazoline derivatives were prepared via the reaction of various chalcones with hydrazine hydrate in ethanol. A group of NO-donating-2-pyrazoline derivatives were synthesized by carrying a nitrate ester group or an oxime group onto the prepared pyrazoline derivatives through different spacers. The prepared compounds were evaluated for their anti-inflammatory activity using carrageenan-induced rat paw edema and compared to a well-known NSAID, indomethacin as a reference drug. The ability of the prepared compounds to induce gastric toxicity was also evaluated. Most of the prepared compounds showed significant anti-inflammatory activity at the injected dose (100mg/kg) but they were safer than indomethacin in regard to gastric toxicity. The incorporation of the NO-donating group into the parent pyrazoline derivatives caused a non-significant reduction in the anti-inflammatory activity while a marked decrease in gastric ulcerations induced by their parent pyrazolines was observed.


Assuntos
Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/farmacologia , Óxido Nítrico/química , Pirazóis/efeitos adversos , Pirazóis/farmacologia , Úlcera Gástrica/induzido quimicamente , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Edema/tratamento farmacológico , Indometacina/efeitos adversos , Indometacina/farmacologia , Masculino , Pirazóis/síntese química , Pirazóis/química , Ratos , Padrões de Referência
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