SYNTHESIS, CHARACTERIZATION AND ANTI INFLAMMATORY ACTIVITY OF NOVEL QUINOXALINE DERIVED CHALCONES

Objective: Quinoxaline derivatives were reported with wide range of biological activities. Hence it was planned to synthesize and screen for their anti inflammatory (in vivo) activity.Methods: Orthophenylene diamine was reacted with oxalic acid to form quinoxaline 2, 3 dione. Quinoxaline-2, 3 (1H, 4H)-dione was chlorinated by using Phosphorousoxytrichloride (POCl3) in dimethyl formamide, to form 2, 3- dichloroquinoxaline. This dichloride compound was reacted with 4 amino acetophenone in DMF, refluxed for 5 hours to form 1-(4-(3-chloroquinoxalin-2-ylamino) phenyl) ethanone. Similarly 1-(4-(3-chloroquinoxalin-2-ylamino) phenyl) ethanone was reacted with corresponding aromatic aldehydes to form quinoxaline derived chalcone by Claisen Schmidt reaction. Characterization all the compounds was performed by IR, 1H NMR and Mass spectroscopic data and screened for anti- inflammatory activity by carrageenan- induced paw edema method.Results: The anti inflammatory data suggested that compounds QCAC 2, 6, 8, 9, 10 and 12 showed significant activity and rest of the compounds exhibited moderate activity compared to the standard compoundConclusion: The compounds bearing nitro, chloro and methoxy groups have shown prominent activity when compared to compounds without these groups.Â

The Importance of a Critical Protonation State and the Fate of the Catalytic Steps in Class A β-Lactamases and Penicillin-binding Proteins

b-Lactamases and penicillin-binding proteins are bacterial enzymes involved in antibiotic resistance to b-lactam antibiotics and biosynthetic assembly of cell wall, respectively. Members of these large families of enzymes all experience acylation by their respective substrates at an active-site serine as the first step in their catalytic activities. A Ser-X-X-Lys sequence motif is seen in all these proteins and crystal structures demonstrate that the side chain functions of the serine and lysine are in contact with one another. Three independent methods were used in this report to address the question of the protonation state of this important lysine (Lys73) in the TEM-1 b-lactamase from Escherichia coli. These techniques included perturbation of the pKa of Lys73 by the study of the g-thialysine-73 variant and the attendant kinetic analyses, investigation of the protonation state by titration of specifically labeled proteins by nuclear magnetic resonance and by computational treatment using the thermodynamic integration method. All three methods indicated that the pKa of Lys73 of this enzyme is attenuated to 8.0-8.5. It is argued herein that the unique ground-state ion pair of Glu166 and Lys73 of class A b-lactamases has actually raised the pKa of the active site lysine to 8.0-8.5 from that of the parental penicillin-binding protein. Whereas we cannot definitively rule out that Glu166 activates the active site water, which in turn promotes Ser70 for the acylation event, such as proposed earlier, we would like to propose as a plausible alternative for the acylation step the possibility that the ion pair would reconfigure to the protonated Glu166 and unprotonated Lys73. As such, unprotonated Lys73 could promote serine for acylation, a process that should be shared among all active-site-serine b-lactamases and penicillin-binding proteins

Drinking Water Safety & Security Planning (DWSSP) Structured Follow - up Implementation Guide

The International WaterCentre (IWC) at Griffith University, in partnership with The University of the South Pacific (USP), have prepared this Implementation Guide following pilot testing with the Department of Water Resources (DoWR) and Vanuatu Red Cross (VRC) in five villages in the Shefa province, Republic of Vanuatu. Research shows that Drinking Water Safety & Security Planning (DWSSP) has mixed results, with community Implementation Plans often not being progressed by communities due to a lack of ownership and collective action. As with community water management more generally, communities require some sort of follow-up support. This guide contains five targeted activities designed to assist communities to re-engage with their Implementation Plans. This DWSSP follow-up activities are especially designed for communities whose DWSSP Plans have stalled, and who may not have received some follow-up visits since the initial DWSSP intervention. This is not intended to be the only form of follow-up support provided to communities

Direct rate measurements of eruption plumes at Augustine volcano: A problem of scaling and uncontrolled variables

The March–April 1986 eruption of Augustine Volcano, Alaska, provided an opportunity to directly measure the flux of gas, aerosol, and ash particles during explosive eruption. Most previous direct measurements of volcanic emission rates are on plumes from fuming volcanoes or on very small eruption clouds. Direct measurements during explosive activity are needed to understand the scale relationships between passive degassing or small eruption plumes and highly explosive events. Conditions on April 3, 1986 were ideal: high winds, clear visibility, moderate activity. Three measurements were made: 1) an airborne correlation spectrometer (Cospec) provided mass flux rates of SO2; 2) treated filter samples chemically characterized the plume and 3) a quartz crystal microcascade impactor provided particle size distribution. Atmospheric conditions on April 3 caused the development of a lee wave plume, which allowed us to constrain a model of plume dispersion leading to a forecast map of concentrations of SO2 at greater distances from the vent. On April 3, 1986, the emission rate of SO2 at Augustine was 24,000 t/d, one of the largest direct volcanic rate measurements yet recorded with a Cospec. The results, coupled with analytical results from samples simultaneously collected on filters, allow us to estimate HCl emissions at 10,000 t/d and ash eruption rate at 1.5×106 t/d. Based on other data, this ash eruption rate is about 1/50 of the maximum rate during the March–April activity. Filter samples show that the gas:aerosol proportions for sulfur and chlorine are about 10:1 and 4:1, respectively. By contrast, measurements of Augustine\u27s plume, together with ground-based gas sampling in July 1986 when the volcano was in a posteruptive fuming state, are 380 t/d SO2 and approximately 8000 t/d HCl with no ash emission. The observations of large Cl releases at Augustine support the Cl abundance conclusions of Johnston (1980) based on study of melt inclusions in the 1976 lavas. The results reinforce the need for more measurements during eruptions and for better understanding of scaling of volcanic emissions of various eruptive components

Aminoglycoside Resistance Rates, Phenotypes, and Mechanisms of Gram-Negative Bacteria from Infected Patients in Upper Egypt

With the re-emergence of older antibiotics as valuable choices for treatment of serious infections, we studied the aminoglycoside resistance of Gram-negative bacteria isolated from patients with ear, urinary tract, skin, and gastrointestinal tract infections at Minia university hospital in Egypt. Escherichia coli (mainly from urinary tract and gastrointestinal tract infections) was the most prevalent isolate (28.57%), followed by Pseudomonas aeruginosa (25.7%) (mainly from ear discharge and skin infections). Isolates exhibited maximal resistance against streptomycin (83.4%), and minimal resistance against amikacin (17.7%) and intermediate degrees of resistance against neomycin, kanamycin, gentamicin, and tobramycin. Resistance to older aminoglycosides was higher than newer aminoglycoides. The most common aminoglycoside resistance phenotype was that of streptomycin resistance, present as a single phenotype or in combination, followed by kanamycin-neomycin as determined by interpretative reading. The resistant Pseudomonas aeruginosa strains were capable of producing aminoglycoside-modifying enzymes and using efflux as mechanisms of resistance. Using checkerboard titration method, the most frequently-observed outcome in combinations of aminoglycosides with β-lactams or quinolones was synergism. The most effective combination was amikacin with ciprofloxacin (100% Synergism), whereas the least effective combination was gentamicin with amoxicillin (53.3% Synergistic, 26.7% additive, and 20% indifferent FIC indices). Whereas the studied combinations were additive and indifferent against few of the tested strains, antagonism was never observed. The high resistance rates to aminoglycosides exhibited by Gram-negative bacteria in this study could be attributed to the selective pressure of aminoglycoside usage which could be controlled by successful implementation of infection control measures

Critical review on biofilm methods

Biofilms are widespread in nature and constitute an important strategy implemented by microorganisms to survive in sometimes harsh environmental conditions. They can be beneficial or have a negative impact particularly when formed in industrial settings or on medical devices. As such, research into the formation and elimination of biofilms is important for many disciplines. Several new methodologies have been recently developed for, or adapted to, biofilm studies that have contributed to deeper knowledge on biofilm physiology, structure and composition. In this review, traditional and cutting-edge methods to study biofilm biomass, viability, structure, composition and physiology are addressed. Moreover, as there is a lack of consensus among the diversity of techniques used to grow and study biofilms. This review intends to remedy this, by giving a critical perspective, highlighting the advantages and limitations of several methods. Accordingly, this review aims at helping scientists in finding the most appropriate and up-to-date methods to study their biofilms.The authors would like to acknowledge the support from the EU COST Action BacFoodNet FA1202

Design, Synthesis, Biological Evaluation, and Structure–Activity Relationships of Substituted Phenyl 4-(2-Oxoimidazolidin-1-yl)benzenesulfonates as New Tubulin Inhibitors Mimicking Combretastatin A-4

International audienc