An efficient, mild and metal free l-proline catalyzed construction of fused pyrimidines under microwave conditions in water.

One-pot condensation of 4-hydroxy coumarins, aldehydes and urea/thiourea to build C-C and C-N bonds is described. Fused pyrimidines have been synthesized under mild reaction conditions using l-proline. The protocol has been performed rapidly and efficiently in water under metal free conditions. Heterocyclic derivatives have been synthesized using the present methodology and avoid the use of hazardous solvents over conventional organic solvents. A proposed mechanism could be established for three component reactions. The present study reveals the first case in which l-proline has been explored as a homogeneous catalyst in the synthesis of fused pyrimidines in water under microwave irradiation. This synthesis involves simple workup and acceptable efficiency. The most notable feature of this protocol is the ability of the catalyst to influence asymmetric induction in the reaction.

Metal-Free Construction of Fused Pyrimidines via Consecutive C-C and C-N Bond Formation in Water.

A facile and efficient protocol has been developed for mild construction of fused pyrimidines via l-proline-catalyzed reaction of 4-hydroxy coumarins, aldehydes, and 2-aminobenzothiazoles/urea. The reaction has been carried out rapidly and efficiently in water under mild and metal-free conditions. Current etiquette has efficiently synthesized the heterocycles and avoids the use of hazardous solvents over conventional organic solvents. A plausible reaction mechanism has been established in this study. This study represents the first case in which l-proline as a homogeneous catalyst has been explored in the synthesis of fused pyrimidines in water in view of simple procedure and acceptable efficiency. This method gives the target product in excellent yield with ease of workup.

Sustainable Synthesis and Characterization of Ni-Al-Containing Double-Layered Nanocatalysts and Their Catalytic Activity.

Sustainable synthesis of Ni-Al double-layered catalysts by the coprecipitation method is described. Synthesized double-layered catalysts have been characterized by X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared, and thermogravimetric analyses, which confirmed a hydrotalcite-like structure. In addition, the impact of aging time and temperature on the activity of catalyst has been investigated. Furthermore, it has been confirmed by SEM and TEM analyses that the recovered catalyst has retained its structure. It has also been observed that the prepared material has potency to catalyze the reaction without loss in the yield. To explore the reactivity of the material, the catalyst has been examined in the synthesis of N-(2-hydroxyphenyl)benzamide under solvent-free conditions. The overall process afforded the product with high purity and high yields within short time.

One-pot facile and mild construction of densely functionalized pyrimidines in water via consecutive C-C and C-S bonds formation.

Fused pyrimidines composed of alternating heteroatoms and a pyrimidine moiety were synthesized efficiently using readily available starting material 4-hydroxycoumarin, aromatic aldehydes, and urea/thiourea at room temperature. Acid, metal salts, and surfactants were screened for their influence on catalytic activity in three-component reactions and sodium lauryl sulphate (SLS) was used as the best catalyst with different concentrations. Screening results of catalyst loading from our investigation showed that good to excellent yields were obtained with 10 mol%. Our method efficiently synthesized heterocycles and avoided the use of hazardous solvents and conventional organic solvents. Our procedure which involves a surfactant is operationally simple, environmentally benign, has excellent yields, short reaction times, and synthetically is as efficient as conventional procedures using organic solvents.

Structure activity relationship, cytotoxicity and evaluation of antioxidant activity of curcumin derivatives.

Series of curcumin derivatives/analogues were designed and efficient method for synthesis thereof is described. All the synthesized compounds have been screened for their cytotoxicity and evaluated their antioxidant activity. Cytotoxicity effect has been evaluated against three cell lines Hep-G2, HCT-116 and QG-56 by MTT assay method. Structure activity relationship has revealed that particularly, compound 3c, (IC50 value 6.25 µM) has shown better cytotoxicity effect against three cell lines. According to results of SAR study, it was found that 4H-pyrimido[2,1-b]benzothiazole derivatives (2e and 2f), pyrazoles (3a, 3b, 3c and 3d) benzylidenes (4d) exhibited better antioxidant activity than curcumin. A correlation of structure and activities relationship of these compounds with respect to drug score profiles and other physico-chemical properties of drugs are described and verified experimentally.

Biological activity, design, synthesis and structure activity relationship of some novel derivatives of curcumin containing sulfonamides.

Five series of curcumin derivatives with sulfonamides 3a-3e, 4a-4e, 5a-5e, 6a-6e and 7a-7e have been synthesized and evaluated for in vitro antibacterial activity against selected medically important gram-(+) and gram-(-) bacterial species viz. Staphylococcus aureus, Bacillus cereus, Salmonella typhi, Pseudomonas aeruginosa and Escherichia coli, and antifungal activity against few pathogenic fungal species viz. Aspergillus niger, Aspergillus flavus, Trichoderma viride and Curvularia lunata. The cytotoxicity has been determined by measuring IC50 values against human cell lines HeLa, Hep G-2, QG-56 and HCT-116. Among the compounds screened, 3a-3e showed the most potent biological activity against tested bacteria and fungi. Compounds 3a-3e displayed higher cytotoxicity than curcumin. The curcumin derivatives were also evaluated for in vivo anti-inflammatory activity. In contrast, the compounds 6a-6e and 7a-7e showed dramatically decrease in biological activity.

Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma.

The impact of bone marrow (BM) GD2-positive cells on survival has been evaluated in 145 Italian children with localised neuroblastoma (NB) evaluated at diagnosis by anti-GD2 immunocytochemistry. Nineteen of these (13.1%) were found to be BM GD2-positive, with the number of positive cells ranging between 1 and 155 out of 1 x 10(6) total cells analysed. Seven/19 (38.8%) GD2-positive vs 12/126 (9.5%) GD2-negative patients relapsed. The 5-year event-free survival (EFS) and overall survival of the GD2-positive patients was significantly worse than that of the GD2-negative ones (62.2 vs 89.9%, P<0.001; and 74.9 vs 95.9%, P=0.005, respectively). GD2 positivity was not associated to other known risk factors, and in particular to Myc-N amplification and 1p deletion. Among Myc-N-negative patients, the EFS of those negative for both GD2 and 1p deletion was significantly better than in children positive for either one of these two markers (EFS=96.9 vs 66.0%, P<0.001). In conclusion, GD2 positivity may represent a prognostic marker for patients with non-metastatic NB without Myc-N amplification, and its combination with genetic alterations might help identifying patients that require a more careful follow-up.

[Neurological disorders in a pediatric emergency room: Epidemiology and clinical aspects]. / La patologia neurologica in un pronto soccorso pediatrico: epidemiologia e clinica.

AIM: The aim of this study was to demonstrate how important neurological disorders are in the organization of services and education of staff in a pediatric emergency room. The first objective was to collect and review data in pediatric emergency care; based on an analysis of these data, the second objective was to design an organizational plan for emergency services to be developed in this setting. METHODS: We used the ICD IX system to search our computerized database created in 2000 and to select diagnoses from the medical records of patients who came to our emergency room with neurological symptoms. Because the system is not yet comprehensive and because this was a retrospective study, we had to select the bulk of the diagnoses following the formulation each of us had given at patient discharge. While this raised the risk of data spread, it still permitted us to identify certain characteristics of the disorders that were particularly useful for classifying their etiopathogenesis. RESULTS: Selected were 2.630 neurological patients that had been discharged or admitted to our unit (2.7% of all admissions). The patients were stratified by disorder and admission code number. Specific disorders of major impact, the clinical approach to their treatment and etiology were reviewed in detail. CONCLUSIONS: The results provide evidence that acute neurological disorders command the immediate attention of the emergency room physician and require prompt diagnosis.

Transcutaneous oxygen pressure measured at two different electrode core temperatures in healthy volunteers and patients with arterial occlusive disease.

The influence of two different electrode core temperatures on transcutaneous oxygen pressure (tcPO2) was studied in ten probands and 28 patients with peripheral arterial occlusive disease. Hyperaemisation of skin by an electrode core temperature of 44 degrees C reflects local hyperaemia flow and can be reproduced constantly. At 37 degrees C low tcPO2 values are recorded which are in good accordance with mathematically calculated capillary dome PO2. According to great physiological alterations in skin perfusion tcPO2 (37 degrees C) varies in wide ranges. This mode of measurement is well suited to study physiological autoregulation mechanisms or the influence of drugs on skin perfusion. The herein reported results are: forefoot tcPO2 (37 degrees C, 44 degrees C) in volunteers is significantly higher than in patients; forefoot tcPO2 (37 degrees C, 44 degrees C) of patients with diabetes mellitus is significantly higher than in nondiabetics; prestenotic tcPO2 (37 degrees C, 44 degrees C) is about two times higher than poststenotic tcPO2 (37 degrees C, 44 degrees C); tcPO2 (37 degrees C) in probands decreased significantly during occlusion of the venous circulation; tcPO2 (44 degrees C) increased in probands and patients when standing up; however, tcPO2 (37 degrees C) decreased in healthy persons and increased in patients when standing up; after a 5-min suprasystolic cuff occlusion of the arterial circulation there was a four- to six-fold increase of tcPO2 (37 degrees C) which indicates reactive skin capillary flow. In conclusion tcPO2 (37 degrees C) permits measurement of relative changes of skin capillary flow under physiological conditions so that autoregulating mechanisms can be studied.

Voluntary consumption of alcohol by baboons. Effects of flavor, concentration and temperature of solution.

Nonrestrained, group-housed baboons drank the greatest amounts of alcohol when it was presented as a 10% to 20% solution in cold fruit juice.