Regioselective synthesis and antitumor screening of some novel N-phenylpyrazole derivatives

The versatile, hitherto unreported 4-acetyl-5-methyl-1-phenyl-3-phenylcarbamoyl-1H-pyrazole (3) was prepared via the reaction of 2-(2-phenylhydrazono)-2-chloro-N-phenylacetamide with pentan-2,4-dione in the presence of sodium ethoxide. Reaction of 3 with dimethylformamide-dimethylacetal (DMF-DMA) furnished the corresponding 4-[(E)-3-(dimethylamino)acryloyl]-5-methyl-1-phenyl-3-phenylcarbamoyl-1H-pyrazole (5). The latter product underwent regioselective 1,3-dipolar cycloaddition with some nitrilimines to afford the non-isolable dihydropyrazole intermediates which then lose dimethylamine yielding the corresponding pyrazole derivatives. The preliminary screening for the antitumor activity of all newly synthesized compounds was carried out against Ehrlich Ascites Carcinoma tumor cells.     

Synthesis of new N-phenylpyrazole derivatives with potent antimicrobial activity

The versatile synthons 4-(2-bromoacetyl)-5-methyl-1-phenyl-3-phenylcarbamoyl-1H-pyrazole (3) and 4-[(E)-3-(dimethylamino)acryloyl]-5-methyl-1-phenyl-3-phenylcarbamoyl-1H-pyrazole (2) were used as precursors for the synthesis of a series of phenylpyrazoles with different aromatic ring systems at position 4. The antimicrobiological evaluation of the newly synthesized compounds was carried out in vitro assays for antifungal and antibacterial activities. Amongst the tested compounds, 4-acetyl-5-methyl-1-phenyl-3-phenylcarbamoyl-1H-pyrazole (1), 4-[(E)-3-(dimethylamino)acryloyl]-5-methyl-1-phenyl-3-phenylcarbamoyl-1H-pyrazole (2), 4-(2-bromoacetyl)-5-methyl-1-phenyl-3-phenylcarbamoyl-1H-pyrazole (3) and 4-(2-aminothiazol-4-yl)-5-methyl-1-phenyl-3-phenylcarbamoyl-1H-pyrazole (17) showed interesting antimicrobial properties. In particular, all tested compounds produced inhibitory effects against pathogenic yeast (Candida albicans) similar or superior to those of reference drug. In addition, compound 3 showed excellent activity against pathogenic mould (Aspergillus). From structure-activity relationship (SAR) point of view, the attachment of bromoacetyl moiety to pyrazole ring can be considered as a breakthrough in developing a new therapeutic antifungal agent related to phenylpyrazole system.     

Kiwifruit ameliorates gentamicin induced histological and histochemical alterations in the kidney of albino mice

Gentamicin is an antibiotic used worldwide for treating Gram-negative bacterial infections. Gentamicin causes nephrotoxicity in up to 25% of therapeutic cases owing to increased production of free radicals. Kiwifruit are nutrient-dense fruits that have proven effective for ameliorating many pathological conditions caused by oxidative stress. We investigated the possible prophylactic and therapeutic effects of kiwifruit on the changes in renal histology and histochemistry caused by gentamicin. Intramuscular injection of mice with gentamicin for 10 consecutive days was nephrotoxic as indicated by epithelial vacuolization, glomerular atrophy and tubular necrosis. Necrotic tubule cells lost most of their polysaccharides and structural proteins. Co-administration of kiwifruit with gentamicin prevented nephrotoxic changes to a modest degree. When administered subsequent to gentamicin intoxication, kiwifruit ameliorated significantly the histological and histochemical alterations caused by gentamicin. Our findings support the use of kiwifruit in cases of acute renal injury due to gentamicin.     

A Synchronous Co-Allocation Mechanism for Grid Computing Systems

Grid computing systems are emerging as a computing infrastructure that will enable the use of wide-area network computing systems for a variety of challenging applications. One of these is the ever increasing demand for multimedia from users engaging in a wide range of activities such as scientific research, education, commerce, and entertainment. To provide an adequate level of service to multimedia applications, it is often necessary to simultaneously allocate resources including predetermined capacities from interconnecting networks to the applications. The simultaneous allocation of resources is often referred to as co-allocation in the Grid literature. In this paper, we formally define the co-allocation problem and propose a novel scheme called synchronous queuing (SQ) for implementing co-allocation with quality of service (QoS) assurances in Grids. Unlike existing approaches, SQ does not require advance reservation capabilities at the resources. This enables an SQ-based approach to over subscribe the resources and hence improve resource utilization. The simulation studies performed to evaluate SQ indicate that it outperforms an QoS-based scheme with strict admission control by a significant margin.     

A Comparative GC/MS Analysis of Citrus Essential Oils: Unveiling the Potential Benefits of Herb-Drug Interactions in Preventing Paracetamol-Induced Hepatotoxicity

Our study aimed to test the potential of Citrus oils in protecting against paracetamol (PAR)-induced hepatotoxicity. The essential oils of Pineapple sweet orange (OO), Murcott mandarin (MO), Red grapefruit (GO), and Oval kumquat (KO) were investigated using gas chromatography coupled with mass spectrometry (GC/MS). Twenty-seven compounds were identified, with monoterpene hydrocarbons being abundant class. d-Limonene had the highest percentage (92.98 %, 92.82 %, 89.75 %, and 94.46 % in OO, MO, GO, and KO, respectively). Hierarchical cluster analysis (HCA) and principal components analysis (PCA) revealed that octanal, linalool, germacrene D, and d-limonene were the principal discriminatory metabolites that segregated the samples into three distinct clusters. In vitro antioxidant capacities were ranged from 1.2–12.27, 1.79–5.91, and 235.05–585.28 μM Trolox eq/mg oil for 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic (ABTS), ferric-reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC), respectively. In vivo, citrus oils exhibited a significant reduction in alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and nitric oxide (NO). Additionally, there was an increase in glutathione reductase (GSH), and the liver architecture was nearly normal. Molecular docking revealed that d-limonene exhibited a good inhibitory interaction with cytochrome P450 (CYP450) isoforms 1A2, 3A4, and 2E1, with binding energies of −6.17, −4.51, and −5.61 kcal/mol, respectively.     

Cyclic AMP-dependent protein kinase stimulates the formation of polyphosphoinositides in the plasma membranes of different blood cells

Plasma membrane preparations from lymphocytes, platelets and red cells were phosphorylated in the presence of [gamma-32 P]ATP. The dissociated catalytic subunit of cyclic AMP-dependent protein kinase increased the 32P-labelling of proteins and polyphosphoinositides in lymphocyte, platelet and in some red cell membranes. In the majority of red cell membrane preparations the 32P-labelling of proteins and polyphosphoinositides seemed to be stimulated by the catalytic subunit of the endogenous protein kinase, since the phosphorylation was not increased by the addition of the catalytic subunit but it was decreased by the heat-stable inhibitor protein of the protein kinase. Different sets of 32P-labelled proteins were shown by SDS-gel electrophoresis in the membranes of the 3 cell types. A 24000-Mr protein was the only one which was phosphorylated by the catalytic subunit in each membrane.     

Influence of extracellular magnesium on the contractile and endothelium-dependent dilatory responses of feline mesenteric arteries.

To clarify the effect of extracellular magnesium on the vascular reactivity of feline isolated mesenteric arteries, the effects of slight alterations in the extracellular magnesium concentration on the contractile and endothelium-dependent dilatory responses were investigated in vitro. The contractions, induced by noradrenaline 10(-8)-10(-5) M, were not affected in the mesenteric artery at low extracellular magnesium (0.8 mM versus to the normal, 1.2 mM). High (1.6 and 2.0 mM) magnesium exerted a modest inhibitory effect on the contractile responses. This depression of the contraction was accompanied with a significant shift to the right in the EC50 value for noradrenaline. The endothelium-dependent relaxations induced by acetylcholine 10(-8)-10(-5) M, were inhibited by high (1.6 and 2.0 mM) magnesium. Lowering of the extracellular magnesium concentration to 0.8 mM, however, failed to alter the dilatory potency of acetylcholine. The depression of the dilatory responses was also accompanied with a shift to the right in the EC50 values for acetylcholine. The present results show, that contractions and endothelium-dependent relaxations of the mesenteric artery are modulated by the extracellular magnesium asymmetrically: slight magnesium deficiency does not affect these responses, whereas elevation of the concentration of this ion inhibits both processes. Extracellular magnesium probably affects rather the binding of these contractile and endothelium-dependent dilatory agonists to their receptors than the calcium influx into the endothelial- and smooth muscle cells in this vessel.     

Evaluation of abundance of aerobic bacteria in the rhizosphere of transgenic and non-transgenic alfalfa lines

Fourteen genetically modified lines of alfalfa (Medicago sativa) containing the gene Ov from Japanese quail, coding for a methionine-rich protein ovalbumin, were evaluated for nodulation ability and concentration of aerobic bacteria in the rhizosphere. The transgenic lines were derived from a highly regenerable genotype Rg9/I-14-22, selected from cv. Lucia. On selective media, a higher concentration of ammonifying bacteria, bacterial spores, denitrifying and nitrifying bacteria were observed in the rhizosphere of transgenic clonesand, on the other hand, lower concentration of cellulolytic bacteria and Azotobacter spp. compared with the rhizosphere of non-transgenic clone SE/22-GT2. A statistically significant difference in the concentration of all the bacterial types was found between samples taken from two types of substrates (i.e. sterile vs. nonsterile). Higher bacterial concentration (measured as colony forming units per g soil dry mass) were observed for all tested groups of culturable bacteria in the non-sterile substrate. The presence of Azotobacter spp. was found only in the rhizosphere of plants grown in non-sterile soil in which the highest number of fertile soil particles (97 %) was observed in transgenic clones SE/22-9-1-12 and SE/22-11-1-1S.1. Concentration of bacteria involved in the N cycle in the soil was increased in the rhizosphere of transgenic clones and decreased in the rhizosphere of non-transgenic plants compared with the average value. In spite of some differences in colony numbers in samples isolated from the root rhizosphere of transgenic and nontransgenic alfalfa plants, we could not detect any statistically significant difference between individual lines.     

Physiology in the oeuvre of a prominent Hungarian medical scientist--Endre H"ogyes.

Endre Hógyes, one of the most prominent and internationally-renown leaders in the field of medical research, especially the treatment of rabies, was born one hundred and fifty years ago in Hungary. E. Hógyes had started his medical and research carrier in 1870. In 1889 he had become vice-president of the Royal Hungarian Society of Natural Sciences and was elected as a member of the Hungarian Academy of Sciences (MTA) and that member of the National Council of Public Health. Scientific carrier of E. Hógyes has always been closely linked to physiological sciences. E Hógyes made a significant contribution to different areas of physiological sciences; his most important scientific publications in this field deal with renal physiology, respitary mechanics, cerebellar function, and associated eye movement. Endre Hógyes was the first to organize Hungarian physiologists into a community. The "Special Physiological Conferences" were initiated within the Hungarian Royal Society of Natural Sciences in 1891. As a token of appretiation, Hungarian physiologists and other medical professionals have announced the year of 1997 as a memorial year of Dr. Endre Hógyes.