1,720,963 research outputs found
Synthesis and biological evaluation of EGFR/HER-2 inhibitors: analogs of 5-substituted-4-anilinoquinazoline and 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile: screening for development of novel PET tracers
No full textThe aim of this project was to synthesize new PET tracers for the imaging of the EGFR/HER-2 expressing tumors and to explore PET-assisted drug discovery approach for novel EGFR/HER-2 inhibitors. To achieve this aim, several research aspects such as design, synthesis, in vitro-in vivo biological evaluation and preliminary PET studies had to be performed. We chose two classes of commercially available anticancer compounds, 5-substitued-anilinoquinazolines (reversible inhibitors) and 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile (irreversible inhibitor). Their analogs were synthesized by different synthetic routes in quantitative yields and characterized by proton NMR and MS. The final compounds were purified > 95% and used for in vitro biological evaluations. The various assays were developed and validated to analyse EGFR and HER-2 kinase inhibitory activities, autophosphorylation inhibition, and cell growth inhibition on a variety of cancer cell lines harboring different EGFR or HER-2 expression levels or mutational status. The results obtained for the two series of compounds were compared with clinical leads (Gefitinib, Erlotinib and EKB-569). The compounds 43 and 47 were found to be the most potent inhibitors among all and compounds 9, 42 and 43 were selected as potential PET tracers. After selection of leads for radiochemistry, the conditions were set up for the different steps involved in the radiochemical synthesis of 18F-labelled radiotracers. The method developed needs further optimization for production of [18F]-9 to maximize the radiochemical yield. Modifications are also required to minimize synthesis time as less as possible. Also, radiochemistry for rest of the compounds remains to be explored. We also intend to use the PET nuclear modality for the therapeutic efficacy analysis of potent promising compounds such as compound 43 and 47
Flavonoids and Related Compounds as Nucleoside Transporter Inhibitors
Full text linkMammalian nucleoside transporters can be classified into two main categories, namely, equilibrative nucleoside transporters (ENTs) and concentrative nucleoside transporters (CNTs). ENTs are ubiquitous, and mediate sodium-independent bi-directional facilitated diffusion nucleoside transport processes. CNTs on the other hand, are secondary active unidirectional transporters that are sodium-dependent. Both the equilibrative and the concentrative nucleoside transporters have several family members which are ENT1 to ENT4 and CNT1 to CNT6. Over the past two decades, important advances in the understanding of nucleoside transporter functions have been made. Identification and molecular cloning of the ENT and CNT families from mammals and protozoan parasites have provided much information about the structure, function, regulation, and tissue and cellular localization. Structure–function analyses of various nucleoside transporter chimeras and mutants have revealed important elements involved in substrate and inhibitor recognition and binding. However, the mechanisms that regulate nucleoside transporters in various tissues and cell types are just beginning to be understood. Because of the ability of these transporters to handle nucleoside analogues used in the treatment of patients with cancer and viral diseases, ongoing research should allow the design of more specifically targeted new compounds or improvements to existing drugs. New drugs are welcome not only in the treatment of cancer and viral diseases, but also in cardiovascular disorders and parasitic infections. Due to the absence of crystal structures and limited information regarding the active sites of nucleoside transporters, the designing of novel inhibitors is confined to ligand-based methods. In an effort to search for novel classes of inhibitors other than the existing ones, a series of 95 different flavone and flavone-like compounds was screened against concentrative nucleoside transporters (CNT 1, 2 and 3) and equilibrative nucleoside transporters (ENT 1 and 2). The results obtained in the form of IC50 values were further utilized to perform quantitative structure–activity relationship studies which indeed helped to understand the effects of different functionalities in the inhibition of nucleoside transporters. The validated 3D-QSAR models were used for design and activity prediction of new compounds. Pharmacophore hypotheses were also generated for hCNT3 using the PHASE pharmacophore mapping program to establish structural criteria for inhibitor design, and for database searching to find new hit molecules. Additionally, fifteen compounds were selected based on SAR and screened for equilibrative nucleoside transporter inhibition for validation of QSAR models. One novel compound, XI was designed with reduced complexity in further attempts to identify the ENT pharmacophore. But the synthetic route followed to prepare compound XI, resulted in the synthesis of compounds XII and XIII, which were evaluated as a mixture and exhibited substantial inhibitory activity against hENT1, but had no significant effect on hENT2 or hCNT3.This work has identified a novel class of CNT and ENT nucleoside transporter inhibitors and delineated structural determinants of potency and transporter subtype selectivity
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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