1,721,041 research outputs found
Design, synthesis and antiviral evaluation of pyrazole and pyrazoline derivatives as novel inhibitors of flavivirus and pestivirus replication
Full text linkThe Flaviviridae family represents a large group of viral pathogens which are divided, according to the current taxonomy, in four genera: Flavivirus (type spe¬cies, yellow fever virus (YFV)), Hepacivirus (type species, hepatitis C virus (HCV)), Pestivirus (type species, bovine virus diar¬rhea (BVDV)) and Pegivirus (type species, hepatitis G virus (HGV)). Despite the majority of these viruses are responsible for a wide range of severe diseases in humans and animals, specific antiviral therapies are currently available only for the treatment of HCV infections. The global, social and economic impact due to morbidity and even mortality associated with these infections, urgently demands effective therapeutic interventions.
Following the researches undertaken in our laboratory on heterocyclic compounds with antiviral activity, the design, synthesis and antiviral evaluation of new classes of pyrazole and pyrazoline derivatives with potent and selective anti-Flavivirus or anti-BVDV activity is described in the present PhD thesis.
By the antiviral screening of an in house library of compounds, N-(1,3-diphenyl-1H-pyrazol-4-yl)methyl]anilines were identified as a new class of potent and selective inhibitors of human respiratory syncytial virus (RSV) replication. Some derivatives were also endowed with a moderate activity against BVDV and against significant human pathogens belonging to the Flavivirus genus such as YFV, Dengue Virus (DENV) and West Nile Virus (WNV). The hit compounds exhibited activity in the micromolar range coupled with low cytotoxicity (CC50 > 100 μM) against the cell lines (MDBK and BHK-21) utilized for the in vitro assays. Therefore, the systematic modification of all the portions of the molecular scaffold was planned, in order to identify more active compounds and to maintain the low cytotoxicity of the hit compounds. In particular, potent and selective inhibitors of YFV replication were obtained by replacement of the 1-phenyl ring with the 1-phenylsulfonyl moiety.
Pursuing our research on anti-Flaviridae compounds, we also devoted our attention to pyrazoline analogues of previously studied pyrazole derivatives. The antiviral screening of the novel series of 1,3,5-trisubstituted pyrazolines has led to the identification of new hit compounds with promising activity against YFV and BVDV.
Time of addition experiments were performed to determine the possible step(s) in YFV replication cycle that is inhibited by two 1,3,5-triphenyl-pyrazolines selected for their high anti-YFV potency and selectivity. The results of these studies showed that both compounds exhibited maximal inhibition when added in the pretreatment of BHK-21 cells or during infection of cell cultures with YFV. A similar behavior was observed for the reference inhibitor 6-Azauridine, at higher concentrations. However, further investigations are necessary for the identification of the anti-YFV target of these pyrazoline derivatives
Stereoselective synthesis of alpha-aryl-2-benzofuranmethanamines and alpha-aryl-1H-indole-2-methanamines through palladium-mediated annulation of chiral alpha-arylpropargylamines
No full textThe title compounds, valuable chiral synthons for the synthesis of biologically active compounds, have been prepared in good yield and with high stereoselectivity through palladium-catalyzed heteroannulation of 2-iodophenol or 2-iodo-N-mesylaniline with enantiomerically pure or enriched alpha-arylpropargylamines. (C) 2000 Elsevier Science Ltd. All rights reserved
Chiral azole derivatives. 4. Enantiomers of bifonazole and related antifungal agents: synthesis, configuration assignment, and biological evaluation
Full text linkThe first synthesis, full stereochem. characterization and biol. evaluation of of both enantiomers of bifonazole (I) and the related II, III and IV are described
Attività sul S.N.C. della 4H 6H-Pirrolo(1,2-a) (4,1) Benzossazepina e di alcuni suoi derivati.
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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