Pharmacophore Mode lingand Virtual Screening to Design the Potential Influenza Virus Endonuclease Inhibitors

Influenza virus endonuclease is an attractive target for antiviral therapy in the treatment of influenza infection. The purpos e of this study is to design a novel antiviral agent with improved biological activities against the influenza virus endonuclease. In this study, chemical feature‐based 3D pharmacophore models were developed from 41 known influenza virus endonuclease inhibitors. The best quantitative pharmacohore model (Hypo 1), which consists of two hydrogen‐bond acceptors and two hydrophobic features, yields the highest correlation coefficient (R = 0.886). Hypo 1 was further validated by the cross validation method and the test set compounds. The application of this model for predicting the activities of 11 known influenza virus endonuclease inhibitors in the test set shows great success. The correlation coefficient of 0.942 and a cross validation of 95;% confidence level prove that this model is reliable in identifying structurally diverse compounds for influenza virus endonuclease inhibition. The most active compound (compound 1) from the training set was docked into the active site of the influenza virus endonuclease as an additional verification that the pharmacophore model is accurate. The docked conformation showed important hydrogen bond interactions between the compound and two amino acids, Lys 134 and Lys 137. After validation, this model was used to screen the NCI chemical database to identify new influenza virus endonuclease inhibitors. Our study shows that the to pranking compound out of the 10 newly identified compounds using fit value ranking has an estimated activity of 0.049 μM. These newly identified lead compounds can be further experimentally validated using in vitro techniques.     

Perception of native and non-native affricate-fricative contrasts: cross-language tests on adults and infants

Previous studies have shown improved sensitivity to native-language contrasts and reduced sensitivity to non-native phonetic contrasts when comparing 6-8 and 10-12-month-old infants. This developmental pattern is interpreted as reflecting the onset of language-specific processing around the first birthday. However, generalization of this finding is limited by the fact that studies have yielded inconsistent results and that insufficient numbers of phonetic contrasts have been tested developmentally; this is especially true for native-language phonetic contrasts. Three experiments assessed the effects of language experience on affricate-fricative contrasts in a cross-language study of English and Mandarin adults and infants. Experiment 1 showed that English-speaking adults score lower than Mandarin-speaking adults on Mandarin alveolo-palatal affricate-fricative discrimination. Experiment 2 examined developmental change in the discrimination of this contrast in English- and Mandarin-leaning infants between 6 and 12 months of age. The results demonstrated that native-language performance significantly improved with age while performance on the non-native contrast decreased. Experiment 3 replicated the perceptual improvement for a native contrast: 6-8 and 10-12-month-old English-learning infants showed a performance increase at the older age. The results add to our knowledge of the developmental patterns of native and non-native phonetic perception.     

Linear response equilibrium

A new periodic pulse sequence employing weak excitation is presented. This type of sequence drives the system into a steady-state with periodic time evolution from which the data can be reconstructed to a spectrum. It is demonstrated that the frequency response of such a sequence can be analyzed using perturbation methods and linear system analysis. A mathematical framework is proposed allowing the frequency response to be tailored by weighting a periodic flip function. The weak excitation level used implies very low specific absorption rates while generating a highly frequency selective signal in the order of 1/T2 with signal strengths comparable to those obtainable with conventional large flip angle balanced steady-state free precession techniques. The concept is illustrated with phantom experiments and in vivo feasibility of water fat separation is shown on human knee images.     

Bioassay-guided purification and identification of antimicrobial components in Chinese green tea extract

The Chinese green tea extract was found to strongly inhibit the growth of major food-borne pathogens, Escherichia coli O157:H7, Salmonella Typhimurium DT104, Listeria monocytogenes, Staphylococcus aureus, and a diarrhoea food-poisoning pathogen Bacillus cereus, by 44-100% with the highest activity found against S. aureus and lowest against E. coli O157:H7. A bioassay-guided fractionation technique was used for identifying the principal active component. A simple and efficient reversed-phase high-speed counter-current chromatography (HSCCC) method was developed for the separation and purification of four bioactive polyphenol compounds, epicatechin gallate (ECG), epigallocatechin gallate (EGCG), epicatechin (EC), and caffeine (CN). The structures of these polyphenols were confirmed with mass spectrometry. Among the four compounds, ECG and EGCG were the most active, particularly EGCG against S. aureus. EGCG had the lowest MIC90 values against S. aureus (MSSA) (58 mg/L) and its methicilin-resistant S. aureus (MRSA) (37 mg/L). Scanning electron microscopy (SEM) studies showed that these two compounds altered bacterial cell morphology, which might have resulted from disturbed cell division. This study demonstrated a direct link between the antimicrobial activity of tea and its specific polyphenolic compositions. The activity of tea polyphenols, particularly EGCG on antibiotics-resistant strains of S. aureus, suggests that these compounds are potential natural alternatives for the control of bovine mastitis and food poisoning caused by S. aureus.     

Screening and structural characterization of α-glucosidase inhibitors from hawthorn leaf flavonoids extract by ultrafiltration LC-DAD-MS n and SORI-CID FTICR MS

In vitro α-glucosidase inhibition assays and ultrafiltration liquid chromatography with photodiode array detection coupled to electrospray ionization tandem mass spectrometry (ultrafiltration LC-DAD-ESI-MS ⁿ ) were combined to screen α-glucosidase inhibitors from hawthorn leaf flavonoids extract (HLFE). As a result, four compounds were identified as α-glucosidase inhibitors in the HLFE, and their structures were confirmed to be quercetin-3-O-rha- (1-4)-glc-rha and C-glycosylflavones (vitexin-2″-O-glucoside, vitexin-2″-O-rhamnoside and vitexin) by high-resolution sustained off resonance irradiation collision-induced dissociation (SORI-CID) data obtained by Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS). Several other C-glycosylflavones (vitexin, isovitexin, orientin, isooriention) and their aglycones apigenin and luteolin were evaluated by in vitro assays, and were found to possess strong α-glucosidase inhibitory activities as well. Moreover, the substituent groups on the flavones had a great impact on the enzyme inhibition activity. C-3′-OH of the B-ring of flavones in particular increased the α-glucosidase inhibition activity, whereas C-glycosylations at C-6 or C-8 of the A ring weakened the inhibition activity.     

ChemInform Abstract: On Compound Formation of M′O:M2O3. Part 11. Crystal Structure of BaIn2O4.

Single crystals of the title compound, obtained from a melt after reacting intimate mixtures of BaCO₃ and In₂O₃ at 840 °C (12 h), belong to the monoclinic space group P2₁/a with Z=16.     

ChemInform Abstract: Boron Occupied Condensed Clusters in Ta5Ge3By (y ≈ 0.7).

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.