2-Phenyloxazole-4-carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (K_i) values in the sub-micromolar range and a good selectivity index (K_{i MAO-A}/K_{i MAO-B}>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.     

Current-mode A/D converter

The authors report the design of a new current-mode A/D converter, based on a modified successive-approximations model, in 1.2 μm CMOS technology. The proposed circuit is characterised by good accuracy and fast dynamic performance, low power consumption and small occupation area. SPICE simulations allow the design approach to be validated and the electrical performance of the ADC to be predicted     

The influence of semantic encoding on recognition memory in Alzheimer's disease

Within the framework of the distinction between episodic and semantic memory, it has been argued that these two memory systems are organised in a hierarchical way. The hierarchical hypothesis assumes that episodic memory is a specific subsystem of semantic memory and therefore implies that episodic memory cannot exist without semantic memory. If this hypothesis is correct, it should be expected that patients with impaired semantic memory also have impaired episodic memory. In the present study, two experiments investigated the influence of semantic encoding on recognition memory performance in a population of 20 patients with Alzheimer's disease and 18 normal controls. Both experiments assessed recognition memory for semantically-related items. In Experiment 2, but not in Experiment 1, subjects were explicitly instructed to make a semantic association between the items. Alzheimer's disease patients were impaired, compared to the normal controls, on the recognition memory performance of both experiments. The ability to make a semantic association between two items was significantly and positively correlated with the subjects' performance on the recognition tasks. A further analysis showed that patients who were impaired on the semantic association task did significantly worse on the recognition task of Experiment 2 than normal controls and patients who were unimpaired on the semantic association task. These findings are discussed in the context of memory deficits in Alzheimer's disease, and are interpreted as supporting the view that episodic memory for an item is affected by the level of semantic awareness of that same item.     

Development of New Sulphonyl Resin from Modification of Commercial Resin

Summary This article deals with the handy synthesis of sulfonyl resins, which were produced by the treatment of a commercial sulfonic resin (Lewatit VPOC1812^® based at divinylbenzene (DVB) and styrene (STY). The preliminary chemical modification was based on the reaction of the Lewatit VPOC1812^® with thionyl chloride aiming to produce the sulfonyl chloride groups. The best conditions to obtain the sulfonyl chloride groups were: SOCl₂/SO₃H (molar ratio) =13 at 79 °C during 72 h. The resin chlorinated was afterward treated with urea, thiourea or guanidine. The functionalized resins with urea, thiourea or guanidine were produced with 56, 68 and 93% yield, respectively. The commercial and modified resins were characterized by apparent density, swelling degree, elemental analysis (CHNS), FTIR, optical microscopy (OM) and scanning electron microscopy (SEM).     

Drug Release from Lipogels According to Gelling Conditions and Mechanical Treatment

The release rate of a drug dissolved in the liquid phase of lipogels may be greatly affected by the type and concentration of gelling agent and by processing conditions and mechanical treatment of the ointment. These differences in release rate are reduced after application of mechanical stress comparable with the strain exerted on the ointment during application to the skin. Therefore, changes in the concentration of gelling agents used to achieve suitable consistency and manufacturing and packing processes that meet industrial and marketing requirements do not appear to exert a practical influence on drug availability after application to the skin.     

Effect of maillard reaction volatile products on lipid oxidation

Maillard reaction volatile compounds (MRV), prepared by heating a glucose-glycine solution, were tested as antioxidants in soybean oil (SBO) thermoxidation. The volatiles were transferred into the oil by stripping with a stream of Nitrogen and substituting the atmosphere above the oil with air containing MRV. Standard accelerated oxidation was performed by heating the SBO. Peroxide value measurement and headspace gas Chromatographic analysis were carried out on all the samples. The MRV antioxidant activity was evaluated by determining the effect of the induction period and the kinetic rate constant of peroxide and oxidation volatiles formation. The MRV showed a significant antioxidant activity. The effectiveness was variable depending on MRV transfer method to the oil, and the Maillard reaction extent was related to the browning level of glucose/glycine solution. It was found that the maximum effect of MRV prolonged about three times the induction period and reduced the kinetic rate constant by half in relation to the control sample. MRV affects oxidative stability of soybean oil by lengthening the induction period as well as by decreasing the rate of oxidation at the propagation state and reducing the formation of hexanal.     

XV. Yeast sequencing reports. Isolation and DNA sequence of the STE13 gene encoding dipeptidyl aminopeptidase

We have isolated a mutant which exhibits partial constitutivity for a -specific gene expression in α cells. The wild-type gene was cloned and demonstrated to be allelic to the STE13 gene, which encodes the dipeptidyl aminopeptidase involved in processing of the α-factor prepropheromone. Thus, the mating defect of the ste13 mutations in α cells may result both from the production of incompletely processed α-factor and from the increased expression of a -specific genes. The STE13 open reading frame of 931 amino acids contains a putative membrane-spanning segment near its amino terminus and is 31% identical to a second yeast dipeptidyl aminopeptidase (DAP2). A null mutant of STE13 has been constructed: it is viable and sporulation-proficient. The sequence has been deposited in the GenBank data library under Accession Number L21944.     

Simple high-speed CMOS current comparator

A simple modification to an existing current comparator is proposed, which enables a very low response time to be achieved with a minimal increase in circuit complexity. Circuit simulations allowed the design approach to be validated and the comparator performance to be compared to those of two other existing comparators