Synthesis and in vivo diuretic activity of some novel pyrimidine derivatives

A series of 1,6-dihydropyrimidine-2-amine derivatives and 1,6-dihydropyrimidine-2-thiol derivatives were synthesized by the reaction of substituted 1,3-diphenylprop-2-en-1-one (chalcones) with guanidine hydrochloride and thiourea, respectively. All the synthesized compounds were in good agreement with elemental and spectral data. The synthesized compounds were screened in vivo for diuretic activity. The four compounds 2d, 2e, 3d and 3e, which showed moderate to good diuretic activity, were evaluated for their toxicity studies and none of the compounds showed any toxicity of the liver as compared with control. However, compounds 3e and 3d showed diuretic properties more than that of standard (acetazolamide) and were long acting. Overall, compound 3e, 6-(2,6-dichlorophenyl)-4-(pyridin-2-yl)-1,6-dihydropyrimidine-2-thiol, was found to be the most promising candidate of the series.     

Allelopathic effect of aqueous extracts of three weed species on the growth and leaf chlorophyll content of bread wheat

The purpose of this study was to evaluate the allelopathic effect of weeds (Avena fatua, Melilotus officinalis and Polypogon hissaricus) on germination, growth, dry biomass and chlorophyll concentration of three cultivars of wheat (Ata Habib, Pirsabaq and Serin). In germination test, different concentrations of aqueous extracts (5, 10 and 15?g/l) of the three weeds significantly reduced percent germination; however, 15?g/l extract of M. officinalis resulted in complete failure of germination of cultivar Pirsabaq. In pot culture, root and shoot length, chlorophyll concentration and seedling dry biomass of the three wheat varieties showed differential responses to different weeds. Aqueous extract at 15?g/l of A. fatua increased root and shoot length and dry biomass of cultivar Pirsabaq; however, these parameters were significantly retarded in other two wheat cultivars by extract of weeds. Moisture content of the cultivars did not show any response to allelopathic stress of the weeds. In contrast, chlorophyll concentration in Pirsabaq and Serin was significantly increased by aqueous extract of all the weeds but reduced it in cultivar Ata Habib by 50%. In general, Ata Habib was found to be the most sensitive cultivar to the imposed allelopathic stress. The phytotoxic potential of three weeds was found in the order of A. fatua?>?M. officinalis?>?P. hissaricus.     

Discovery of VEGFR inhibitors through virtual screening and energy assessment

Vascular endothelial growth factor receptor-2 (VEGFR-2) is crucial in promoting tumor angiogenesis and cancer metastasis. Thus, inhibition of VEGFR-2 has appeared as a good tactic for cancer treatment. To find out novel VEGFR-2 inhibitors, first, the PDB structure of VEGFR-2, 6GQO, was selected based on atomic nonlocal environment assessment (ANOLEA) and PROCHECK assessment. 6GQO was then further used for structure-based virtual screening (SBVS) of different molecular databases, including US-FDA approved drugs, US-FDA withdrawn drugs, may bridge, MDPI, and Specs databases using Glide. Based on SBVS, receptor fit, drug-like filters, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of 427877 compounds, the best 22 hits were selected. From the 22 hits, hit 5 complex with 6GQO was put through molecular mechanics/generalized born surface area (MM/GBSA) study and hERG binding. The MM/GBSA study revealed that hit 5 possesses lesser binding free energy with more inferior stability in the receptor pocket than the reference compound. The VEGFR-2 inhibition assay of hit 5 disclosed an IC₅₀ of 165.23 nM against VEGFR-2, which can be possibly enhanced through structural modifications.     

Incidence of aeromonads in samples from an abattoir processing lambs

Two hundred and thirty three samples of lamb carcasses, livers, kidneys and faeces, collected at a local abattoir, were examined to determine the incidence of motile Aeromonas spp. Wash water from the abattoir was also tested. Direct plating on starch ampicillin agar and enrichment in alkaline peptone water were used. The incidence of aeromonads was low. They were detected only after enrichment in 5/47 faecal samples and 11/50 carcass samples. The 41 strains of Aeromonas isolated were identified to species level and 93% of them were able to grow at 5 degrees C. The ability to produce both haemolysin and enterotoxin was species-related and was more common in Aeromonas hydrophila and A. sobria strains than in A. caviae strains.     

Cross sectional study of primary care groups in London: association of measures of socioeconomic and health status with hospital admission rates

ObjectivesTo calculate socioeconomic and health status measures for the primary care groups in London and to examine the association between these measures and hospital admission rates.DesignCross sectional study.Setting66 primary care groups in London, total list size 8.0 million people.ResultsStandardised hospital admission ratios varied from 74 to 116 for total admissions and from 50 to 124 for emergency admissions. Directly standardised admission rates for asthma varied from 152 to 801 per 100 000 (mean 364) and for diabetes from 235 to 1034 per 100 000 (mean 538). There were large differences in the mortality, socioeconomic, and general practice characteristics of the primary care groups. Hospital admission rates were significantly correlated with many of the measures of chronic illness and deprivation. The strongest correlations were with disability living allowance (R=0.64 for total admissions and R=0.62 for emergency admissions, P<0.0001). Practice characteristics were less strongly associated with hospital admission rates.ConclusionsIt is feasible to produce a range of socioeconomic, health status, and practice measures for primary care groups for use in needs assessment and in planning and monitoring health services. These measures show that primary care groups have highly variable patient and practice characteristics and that hospital admission rates are associated with chronic illness and deprivation. These variations will need to be taken into account when assessing performance.     

AgNO3 dependant modulation of glucose mediated respiration kinetics in Escherichia coli at different pH and temperature

The inhibitory role of AgNO₃ on glucose‐mediated respiration in Escherichia coli has been investigated as a function of pH and temperature using Clark‐type electrode, environmental scanning electron microscopy, and computational tools. In the given concentration of bacterial suspension (1 × 10⁸ CFU/ml), E. coli showed an increasing nonlinear trend of tetra‐phasic respiration between 1–133 μM glucose concentration within 20 min. The glucose concentrations above 133 μM did not result any linear increment in respiration but rather showed a partial inhibition at higher glucose concentrations (266–1066 μM). In the presence of glucose, AgNO₃ caused a concentration‐dependent (47–1960 μM) inhibition of the respiration rate within 4 min of its addition. The respiration rate was the highest at pH 7–8 and then was decreased on either side of this pH range. The inhibitory action of AgNO₃ upon bacterial respiration was the highest at 37 °C. The observations of the respiration data were well supported by the altered bacterial morphology as observed in electron microscopic study. Docking study indicated the AgNO₃ binding to different amino acids of all respiratory complex enzymes in E. coli and thereby explaining its interference with the respiratory chain. Copyright © 2016 John Wiley & Sons, Ltd.