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1.
Chem Biodivers ; : e202402031, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39284766

RESUMEN

Methicillin-resistant Staphylococcus aureus (MRSA) is a major contributor to hospital-acquired infections and is highly resistant to treatment. Ongoing research focuses on developing new antimicrobial medications to prevent the spread of resistance. A facile method was employed to efficiently synthesize new pyrazolo[1,5-a]pyrimidines in 84-93% yields by reacting 4-benzyl-1H-pyrazole-3,5-diamine with the respective α,ß-unsaturated ketones. The reaction was carried out in ethanol containing 1.2 equivalents of potassium hydroxide at reflux for 5-6 h. The new products are attached to a para-substituted aryl group with variable electronic properties at pyrazolopyrimidine-C5, in addition to one of three units at C7, namely phenyl, thiophen-2-yl, or furan-2-yl units. A wide spectrum of antibacterial activity was displayed by the new pyrimidines against six different bacterial strains. In general, pyrimidines attached to furan-2-yl units at C7, in addition to another aryl unit at C5, attached to 4-Me or 4-OMe groups, demonstrate significant antibacterial activity, particularly against S. aureus strain. They had MIC/MBC of 2.5/5.1 and 2.4/4.9 µM, respectively, which exceeded that of ciprofloxacin. Moreover, they demonstrate more effective MRSA inhibitory activity than linezolid, with MIC/MBC values up to 4.9/19.7 and 2.4/19.7 µM against MRSA ATCC:33591 and ATCC:43300 strains, respectively.

2.
J Clin Med ; 12(14)2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37510889

RESUMEN

Aortic valve defects are among the most prevalent clinical conditions. A severely damaged or non-functioning aortic valve is commonly replaced with a bioprosthetic heart valve (BHV) via the transcatheter aortic valve replacement (TAVR) procedure. Accurate pre-operative planning is crucial for a successful TAVR outcome. Assessment of computational fluid dynamics (CFD), finite element analysis (FEA), and fluid-solid interaction (FSI) analysis offer a solution that has been increasingly utilized to evaluate BHV mechanics and dynamics. However, the high computational costs and the complex operation of computational modeling hinder its application. Recent advancements in the deep learning (DL) domain can offer a real-time surrogate that can render hemodynamic parameters in a few seconds, thus guiding clinicians to select the optimal treatment option. Herein, we provide a comprehensive review of classical computational modeling approaches, medical imaging, and DL approaches for planning and outcome assessment of TAVR. Particularly, we focus on DL approaches in previous studies, highlighting the utilized datasets, deployed DL models, and achieved results. We emphasize the critical challenges and recommend several future directions for innovative researchers to tackle. Finally, an end-to-end smart DL framework is outlined for real-time assessment and recommendation of the best BHV design for TAVR. Ultimately, deploying such a framework in future studies will support clinicians in minimizing risks during TAVR therapy planning and will help in improving patient care.

3.
Chem Biodivers ; 20(6): e202300546, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37158460

RESUMEN

An efficient protocol was adopted to efficiently prepare three new series of bis(pyrazolo[1,5-a]pyrimidines) linked to different spacers. The new bis(pyrazolo[1,5-a]pyrimidines) were prepared in 80-90 % yields by reacting the respective bis(enaminones) and 4-(4-substituted benzyl)-1H-pyrazole-3,5-diamines in pyridine at reflux temperature for 5-7 h. The new products showed a wide spectrum of antibacterial activity against six different bacterial strains. In general, propane- and butane-linked bis(pyrazolo[1,5-a]pyrimidines), which are attached to 3-(4-methyl- or 4-methoxybenzyl) units, had the best antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values up to 2.5 and 5.1 µM, respectively. Additionally, the previous products demonstrated promising MurB inhibitory activity with IC50 values up to 7.2 µM.


Asunto(s)
Antibacterianos , Pirimidinas , Pirimidinas/farmacología , Antibacterianos/farmacología , Bacterias , Pruebas de Sensibilidad Microbiana , Propano , Relación Estructura-Actividad , Estructura Molecular
4.
Chem Biodivers ; 20(4): e202200518, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36988046

RESUMEN

Two series of piperazine-linked bis(chromene) hybrids that are attached to pyrazole units were synthesized in the current study. Both series are attached to an acyl unit at pyrazole-C3, with one series attached to an acetyl unit and the other to an ethoxycarbonyl unit. A [3+2] cycloaddition protocol was conducted to produce the target hybrids with good yields by reacting the appropriate hydrazonoyl chlorides with chromene-based bis(enaminone) in dioxane containing triethylamine at reflux for 4 h. New hybrids were tested for acetylcholinesterase inhibitory activity at concentrations of 15 and 25 µM, as well as their ability to quench 2,2-diphenylpicrylhydrazyl (DPPH) free radicals at a concentration of 25 µg/mL. In general, the inhibitory activity is related to the electronic properties of the para-substituent that is attached to the arene unit at pyrazole-N1. Furthermore, the acyl unit attached to pyrazole-C3 has a significant effect on the new hybrids' inhibitory activity. At the previous concentrations, the (3-acetylpyrazole)-linked hybrid attached to p-NO2 units demonstrated the best acetylcholinesterase inhibitory activity, with inhibition percentages of 79.7 and 90.2. Furthermore, the previous hybrid demonstrated the most effective DPPH inhibitory activity, with an inhibition percentage of 87.5.


Asunto(s)
Acetilcolinesterasa , Inhibidores de la Colinesterasa , Inhibidores de la Colinesterasa/química , Benzopiranos/química , Relación Estructura-Actividad , Reacción de Cicloadición , Pirazoles/química , Piperazinas/farmacología , Simulación del Acoplamiento Molecular
5.
Chem Biodivers ; 20(4): e202300206, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36950775

RESUMEN

A three-component protocol was established to efficiently synthesize (chromene-thiazole) and related arylazo analogs in good to excellent yields. The desired products were prepared by reacting the appropriate salicylaldehydes, 2-cyanothioacetamide, and chloroacetone or hydrazonyl chlorides. Using piperidine as a mediator in ethanol at 80 °C for 4-6 h, the three-component protocol produce the target hybrids in 87-96 % yields. The newly synthesized products showed a broad range of antibacterial activity. The addition of an arylazo unit at the chromene-C6 position significantly improved the antibacterial activity, while the impact of adding an arylazo group at the thiazole-C5 position varied based on the electronic characteristics of the para-substituted arene unit. Generally, series that is linked to two arylazo units, one at chromene-C6 and the other at thiazole-C5, showed the best activity. Some new hybrids showed effective antibacterial activity than ciprofloxacin with MIC/MBC values up to 1.9/3.9 µM against S. aureus and E. coli. Additionally, they demonstrated better effectiveness against MRSA ATCC:33591 and ATCC:43300 compared to linezolid, with MIC/MBC values up to 4.0/16.1 and 3.9/15.6 µM, respectively. The data predicted for the physicochemical properties, lipophilicity, pharmacokinetics, and drug-likeness of new arylazo-based chromene-thiazole hybrids evaluated by SwissADME. As a result of the above, products that are linked to two arylazo units can be considered drug-like scaffolds.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Staphylococcus aureus , Tiazoles/farmacología , Tiazoles/química , Benzopiranos/farmacología , Benzopiranos/química , Escherichia coli , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química
6.
Saudi Pharm J ; 30(10): 1405-1417, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36387332

RESUMEN

Background: The therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. Hemoglobin tightly binds to NO forming methemoglobin altering the erythrocytic antioxidant defense system. Aim: The principal objective of our research is to show the ameliorating effect of l-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs used in cardiovascular diseases such as oxidative stresses and tolerance. Method: We studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered different concentrations of Isosorbide-5-mononitrate (ISMN) 0.3 mg/kg, 0.6 mg/kg and 1.2 mg/kg. Afterwards, we evaluated the role of l-ascorbic acid against these biochemical changes in cardiac tissues. Results: Chronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of the pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in the myocardium muscles in a dose-dependent manner. Meanwhile, such exposure caused a decline in the enzymatic effect of SOD, GSH and CAT accompanied by a decrease in the level of mitochondrial oxidative stress marker (nrf2) in the myocardium muscles and a decrease in the serum iron and total iron-binding capacity (TIBC) in a dose-dependent manner. Concomitant treatment with l-ascorbic acid significantly diminished these changes for all examined parameters. Conclusion: Chronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to the generation of reactive oxygen species. Using l-ascorbic acid can effectively ameliorate such intoxication to overcome nitrate tolerance.

7.
Arch Pharm (Weinheim) ; 355(10): e2200170, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35853239

RESUMEN

A new series of pyrrole-linked mono- and bis(1,3,4-oxadiazole) hybrids, attached to various arene units, was prepared using a two-step tandem protocol. Therefore, a benzohydrazide derivative was condensed with the appropriate aldehydes in ethanol at 80°C for 60-150 min to give the corresponding N-(benzoylhydrazones). Without isolation, the previous intermediates underwent intramolecular oxidative cyclization in dimethyl sulfoxide at 180°C for 90-200 min in the presence of chloramine trihydrate to afford the target hybrids. The cytotoxicity of all hybrids was examined in vitro against the MCF-7, HEPG2, and Caco2 cell lines. Arene-linked hybrids 4i and 4j, attached to p-nitro and p-acetoxy units, were the most potent ones, with IC50 values ranging from 5.47 to 8.80 and 12.75 to 21.22 µM, respectively, when tested on the above cell lines. At the tested concentrations of 5 and 7.5 µM, hybrid 4i inhibited thymidylate synthase (TS) with the best inhibition percentages of 72.3 and 91.3, whereas hybrid 4j displayed comparable inhibitory activity to the reference pemetrexed. Hybrid 4j had inhibition percentages of 62.7 and 82.6, whereas pemetrexed had inhibition percentages of 59.2 and 80.2, respectively. The capability of hybrids 4i and 4j as potential TS inhibitors is supported by molecular docking studies, while SwissADME predicts their efficacy as drug-like scaffolds.


Asunto(s)
Antineoplásicos , Oxadiazoles , Aldehídos/farmacología , Antineoplásicos/farmacología , Células CACO-2 , Proliferación Celular , Cloraminas/farmacología , Dimetilsulfóxido/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/farmacología , Etanol/farmacología , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Oxadiazoles/farmacología , Pemetrexed/farmacología , Pirroles/farmacología , Relación Estructura-Actividad , Timidilato Sintasa/metabolismo , Timidilato Sintasa/farmacología
8.
Chem Biodivers ; 19(8): e202200338, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35818907

RESUMEN

A two-step tandem protocol was used to prepare new pyrrole and/or arene-linked bis(1,3,4-oxadiazoles) as well as their mono-analogs. The appropriate aldehydes and benzohydrazides were first condensed in ethanol at 80 °C to yield the corresponding N-benzoylhydrazones. Without isolation, the previous intermediates were subjected to a chloramine trihydrate-mediated oxidative cyclization in DMSO at 180 °C to yield the target molecules. The antibacterial potency of the (pyrrole-arene)-linked hybrids exceeded the arene-linked hybrids, and the bis(1,3,4-oxadiazoles) exceeded their mono-analogs against six different ATCC strains. Furthermore, the antibacterial efficacy of bis(1,3,4-oxadiazoles) 11c, and 11f, which are linked to pyrrole, and (p-tolylthio)methyl units, was highest against S. aureus, E. coli, and P. aeruginosa strains. Their MIC ranged between 3.8 and 3.9 µM, while their MBC values ranged between 7.7 and 15.8 µM. Additionally, they showed promising bacterial biofilm inhibitory activity against the same strains tested, with IC50 values ranging from 4.7 to 5.3 µM. They were also effective against MRSA ATCC : 33591, and ATCC : 43300 strains, with MIC, and MBC values ranging from 3.8-7.9 and 7.7-15.8 µM, respectively. When tested against the MCF-10A cell lines, hybrids 11c, and 11f are cytotoxic at concEntrations that are more than 6 and 13-fold higher than their MIC values against the S. aureus, E. coli, and P. aeruginosa strains, respectively. This lends support to both hybrids' potential as safe antibacterial agents.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Antibacterianos/farmacología , Bacterias , Biopelículas , Cloraminas/farmacología , Escherichia coli , Pruebas de Sensibilidad Microbiana , Oxadiazoles/farmacología , Pseudomonas aeruginosa , Pirroles/farmacología , Staphylococcus aureus
9.
Chem Biodivers ; 19(1): e202100500, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34784450

RESUMEN

In this study, an efficient one-pot procedure for preparing a new series of pyrazolo[3,4-b]pyridine-fused pyrimidines was described. The target hybrids were developed through a three-component reaction of 3-amino-1H-pyrazolo[3,4-b]pyridine, benzaldehydes, and acetophenones (molar ratio 1 : 1 : 1). The best conditions for the previous reaction were 2.5 equivalents of barium hydroxide in DMF at 150 °C for 6 h. New bis(pyrimidines) were synthesized in high yields using a similar one-pot reaction protocol with some modifications. Thus, two equivalents of each of the appropriate acetophenones and 3-aminopyrazolopyridine were reacted with one equivalent of the appropriate bis(aldehydes). The reaction was carried out at 150 °C for 8 h using 4.5 equivalents of barium hydroxide in DMF. Repeating the previous reaction with the appropriate bis(acetyl) derivatives and benzaldehydes resulted in good yields of the target bis(pyrimidines). The in vitro cytotoxic activity of new pyrimidines against the MCF-7, HEPG2, and Caco2 cell lines was evaluated using the reference doxorubicin (IC50 values of 4.34-6.97 µM). Hybrid 6h had the best activity against Caco2 and MCF-7 cell lines, IC50 values of 12.62 and 14.50 µM, respectively. The IC50 values for hybrids 6c, 6e, and 6f against MCF-7 and Caco2 cell lines were 23.99-41.69 and 33.14-43.33 µM, respectively. Furthermore, hybrid 6e displayed IC50 value of 20.06 µM HEPG2 cell lines, while the hybrids 6c, 6f and 6h exhibited IC50 values ranging between 26.29-50.51 µM. Furthermore, hybrid 6e had an IC50 value of 20.06 µM for the HEPG2 cell lines, whereas hybrids 6c, 6f, and 6h had IC50 values ranging from 26.29 to 50.51 µM.


Asunto(s)
Antineoplásicos/síntesis química , Compuestos de Bario/química , Pirazoles/química , Piridinas/química , Pirimidinas/química , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Pirazoles/síntesis química , Pirazoles/farmacología , Piridinas/síntesis química , Piridinas/farmacología , Estereoisomerismo , Relación Estructura-Actividad
10.
Biomed Pharmacother ; 135: 111216, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33433352

RESUMEN

Destructive effects of hepatocellular carcinoma (HCC) is enhanced by many cellular mechanisms including activation of fibrosis, inflammation and tumor invasion. Therefore, this study was conducted to investigate the therapeutic effects of iCRT14, ß-catenin blocker, on HCC. In addition, the molecular effects of iCRT14 will be investigated on inflammation, fibrosis and tumor invasion pathways. After inducting HCC in rats, hepatic tissues were used for determination of the expression of ß-catenin, nuclear factor (NF)κB, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, matrix metalloproteinase (MMP)9, transforming growth factor (TGF)-ß1, fibroblast growth factor (FGF)-2 and integrin-ß6. Hepatic tissues were stained with hematoxylin/eosin and with anti-Ki67. Results revealed that iCRT14 significantly increased the survival percent of HCC rats, reduced both α-fetoprotein and average number of nodules. In parallel, hepatic sections from HCC rats stained with hematoxylin/eosin revealed vacuolated cytoplasm and necrotic nodules, which were attenuated by treatment with iCRT14. Finally, treating HCC rats with iCRT14 resulted in reduction of the expression of NFκB, TNF-α, IL-1ß, TGF-ß1, MMP9, FGF-2 and integrin-ß6. In conclusion, iCRT14 treatment exhibited antitumor effects against HCC through impairing ß-catenin signaling pathway. iCRT14 suppressed liver tissue inflammation, fibrosis and angiogenesis, possibly via reducing expression of NFκB, TNF-α, IL-1ß, TGF-ß1, MMP-9, FGF-2.


Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Movimiento Celular/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Piridinas/farmacología , Pirroles/farmacología , Tiazolidinedionas/farmacología , beta Catenina/antagonistas & inhibidores , Animales , Citocinas/genética , Citocinas/metabolismo , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Fibrosis , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad Neoplásica , Neovascularización Patológica , Ratas Sprague-Dawley , Tioacetamida , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Vía de Señalización Wnt , beta Catenina/metabolismo
11.
J Diabetes Res ; 2020: 9408316, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32733971

RESUMEN

The chronic hyperglycemia in diabetes is associated with long-term damage, dysfunction, and failure of different organs. Lack of patient education and knowledge about these complications can worsen the quality of a patient's life. Hence, more efforts are needed to improve patient's education especially in rural areas. Aim. Our objective is to explore the association between demographic variables and the knowledge of self-care practices in type 2 diabetes mellitus. Methods. We used observational cross-sectional descriptive study using a validated self-administered questionnaire in both Arabic and English languages as well. A descriptive correlation design analyzed the questionnaire completed by a convenience sample meeting the inclusion criteria. Results. A total of 100 patients met the inclusion criteria for the analysis out of 3251 patients who completed the questionnaire. The study population has low moderate knowledge in diabetes, moderate knowledge in self-care practices, and good knowledge about complications of nephropathy and cardiovascular disease. No significant association between demographic variables. However, better knowledge observed in male (p = 0.028) and self-care practices with female (p = 0.020). Further, educational status is significantly influencing the knowledge of diabetic patients. Conclusion. The study emphasizing irrespective of demographic variable and the importance of patient education to achieve well glycemic control.


Asunto(s)
Diabetes Mellitus Tipo 2 , Conocimientos, Actitudes y Práctica en Salud , Autocuidado , Factores de Edad , Anciano , Estudios Transversales , Escolaridad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arabia Saudita , Factores Sexuales
12.
Bioorg Chem ; 102: 104094, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32711085

RESUMEN

Novel 1,4-bis[(2-(3-(dimethylamino)-1-oxoprop-2-en-1-yl)benzofuran-5-yl)methyl]piperazine was prepared and used as a key synthon for the this study. Therefore, 1,3-dipolar cycloaddition of this synthon with the appropriate hydrazonyl chlorides afforded a new series of bis(1,3,4-trisubstituted pyrazoles), linked via piperazine moiety. Furthermore, it reacted with hydrazine hydrate and phenyl hydrazine individually to afford the corresponding 1,4-bis[(2-(1H-pyrazolyl)benzofuran-5-yl)methyl]piperazines. Different bacterial strains and cell lines were selected to study the in-vitro antibacterial and cytotoxic activities for the new derivatives. 1,4-Bis[((2-(3-acetyl-1-(4-nitrophenyl)-1H-pyrazole-4-yl)carbonyl)benzofuran-5-yl)methyl]piperazine 5e showed the best antibacterial efficacies with MIC/MBC values of 1.2/1.2, 1.2/2.4 and 1.2/2.4 µM against each of E. coli, S. aureus and S. mutans strains, respectively. In addition, the inhibitory activity of some new bis(pyrazoles) as MRSA and VRE inhibitors were studied. Compound 5e gave the best inhibitory activity with MIC/MBC values of 18.1/36.2, 9.0/18.1 and 18.1/18.1 µM, respectively, against MRSA (ATCC:33591 and ATCC:43300) and VRE (ATCC:51575) bacterial strains, respectively. Compound 5e showed more effective biofilm inhibition activities than the reference Ciprofloxacin. It showed IC50 values of 3.0 ± 0.05, 3.2 ± 0.08 and 3.3 ± 0.07 µM against S. aureus, S. mutans and E. coli strains, respectively. Furthermore, experimental study showed excellent inhibitory activities of 1,4-bis[((2-(3-substituted-1-aryl-1H-pyrazole-4-yl)carbonyl)benzofuran-5-yl)methyl]piperazine derivatives, attached to p-NO2 or p-Cl groups, against MurB enzyme. Compound 5e gave the best MurB inhibitory activity with IC50 value of 3.1 µM. The in-silico study was performed to predict the capability of new derivatives as potential inhibitors of MurB enzyme.


Asunto(s)
Antibacterianos/farmacología , Antineoplásicos/farmacología , Biopelículas/efectos de los fármacos , Deshidrogenasas de Carbohidratos/antagonistas & inhibidores , Antibacterianos/síntesis química , Antibacterianos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Benzofuranos/química , Benzofuranos/farmacología , Deshidrogenasas de Carbohidratos/metabolismo , Línea Celular , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Farmacorresistencia Bacteriana/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Enterococcus faecalis/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Piperazina/química , Piperazina/farmacología , Pirazoles/química , Pirazoles/farmacología , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad
13.
Arch Pharm (Weinheim) ; 353(4): e1900309, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31967349

RESUMEN

Efficient procedures are herein reported for the synthesis of novel hybrid thiazoles via a one-pot three-component protocol. The protocol involves the reaction of novel aldehyde, thiosemicarbazide and halogen-containing reagents in solvent- and catalyst-free conditions. The structures of the new thiazoles were elucidated by elemental analyses and spectroscopic data. The in-vitro antibacterial screening and MurB enzyme inhibition assays were performed for the novel thiazoles. The thiazol-4(5H)-one derivative 6d, with p-MeO, exhibits the best antibacterial activities with minimum inhibitory concentration values of 3.9, 3.9, 7.8, and 15.6 µg/ml against Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus mutans, and Escherichia coli, respectively, as compared to the reference antibiotic drugs. It also exhibits the highest inhibition of the MurB enzyme with an IC50 of 8.1 µM. The structure-activity relationship was studied to determine the effect of the structures of the newly prepared molecules on the strength of the antibacterial activities. Molecular docking was also performed to predict the binding modes of the new thiazoles in the active sites of the E. coli MurB enzyme.


Asunto(s)
Antibacterianos/farmacología , Inhibidores Enzimáticos/farmacología , Escherichia coli/enzimología , Tiazoles/farmacología , Uridina Difosfato N-Acetilglucosamina/análogos & derivados , Antibacterianos/síntesis química , Antibacterianos/química , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Escherichia coli/efectos de los fármacos , Klebsiella pneumoniae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Staphylococcus aureus/efectos de los fármacos , Streptococcus mutans/efectos de los fármacos , Relación Estructura-Actividad , Tiazoles/síntesis química , Tiazoles/química , Uridina Difosfato N-Acetilglucosamina/antagonistas & inhibidores , Uridina Difosfato N-Acetilglucosamina/metabolismo
14.
J Prosthet Dent ; 65(6): 782-6, 1991 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-2072321

RESUMEN

This study evaluated the effects on retention of three metal surface textures and four resin luting materials by measuring the magnitude of the force required for the removal of resin-bonded fixed partial denture retainers. The results of the study indicate that a retainer air-abraded with 250 mu aluminum oxide, used with any of the resins tested, should provide sufficient retention for single pontic posterior resin-bonded fixed partial dentures.


Asunto(s)
Aleaciones de Cromo/química , Resinas Compuestas/química , Recubrimiento Dental Adhesivo , Retención de Dentadura , Grabado Ácido Dental/métodos , Análisis del Estrés Dental , Electroquímica , Estudios de Evaluación como Asunto , Humanos , Ensayo de Materiales , Estrés Mecánico , Propiedades de Superficie , Resistencia a la Tracción
15.
J Prosthet Dent ; 64(2): 127-30, 1990 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-2202812

RESUMEN

The laboratory procedures for making a Hi-ceram porcelain anterior reserve three-quarter crown are described. A core of high-fusing aluminum oxide is used as a coping on which tooth contours are restored with a compatible porcelain. Standard dental laboratory equipment is used and the technique can be quickly learned by any experienced ceramics technician.


Asunto(s)
Óxido de Aluminio , Aluminio , Coronas , Porcelana Dental , Incisivo , Técnica de Colado Dental , Diseño de Dentadura , Humanos , Laboratorios Odontológicos
16.
J Egypt Soc Parasitol ; 20(1): 151-60, 1990 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-2110221

RESUMEN

One hundred and fifty patients with active Schistosomiasis haematobium were chosen from Azizia village an endemic area. 50 healthy controls of the same age and sex groups were chosen. Patients were subjected to complete clinical and laboratory examination. Praziquantel orally in a dose of 40 mg/kg was given to each individual and its therapeutic efficacy was assessed by comparing the results of the previous investigations before and 3 months after treatment. The highest infection intensity was noticed in the small age group (A). There was a statistically significant increase of haematuria in this group, dysunia in middle age (B) and increase frequency of micturition & suprapubic tenderness in older age group (C). Ultrasonography showed partial calcification of bladder in 18% of cases in group A, 28% of cases in group B; in group C the percentage was 32% with 14% hydronephrosis, bladder mass 2%, stone bladder & ureter 6%. After praziquantel therapy there was a statistically significant (1) Reduction in haematuria, dysuria increase frequency and suprapubic tenderness (Z less than 1.96). (2) reduction of mean egg count in urine (3) significant improvement of Hb% (4) bladder calcifications showed partial improvement.


Asunto(s)
Esquistosomiasis Urinaria/epidemiología , Adolescente , Adulto , Niño , Egipto/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Praziquantel/uso terapéutico , Prevalencia , Esquistosomiasis Urinaria/tratamiento farmacológico
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