1,720,971 research outputs found
Synthesis of (−)-Dactylolide and 13-Desmethylene-(−)-dactylolide and Their Effects on Tubulin
No full textAn efficient new synthesis has been elaborated for non-natural (−)-dactylolide ((−)-2) and its 13-desmethylene analogue 4, employing a HWE-based macrocyclization approach with β-keto-phosphonate/aldehyde 19 and the respective 13-desmethylene derivative as the key intermediates. Both (−)-2 and 4 as well as the corresponding C20 alcohols inhibit human cancer cell proliferation with IC50 values in the sub-micromolar range and induce the polymerization of tubulin in vitro
Synthesis of (−)-Dactylolide and 13-Desmethylene-(−)-dactylolide and Their Effects on Tubulin
No full textAn efficient new synthesis has been elaborated for non-natural (−)-dactylolide ((−)-2) and its 13-desmethylene analogue 4, employing a HWE-based macrocyclization approach with β-keto-phosphonate/aldehyde 19 and the respective 13-desmethylene derivative as the key intermediates. Both (−)-2 and 4 as well as the corresponding C20 alcohols inhibit human cancer cell proliferation with IC50 values in the sub-micromolar range and induce the polymerization of tubulin in vitro
Optimization of a Benzoylpiperidine Class Identifies a Highly Potent and Selective Reversible Monoacylglycerol Lipase (MAGL) Inhibitor
Full text linkMonoacylglycerol lipase (MAGL) is the enzyme degrading the endocannabinoid 2-arachidonoylglycerol, and it is involved in several physiological and pathological processes. The therapeutic potential of MAGL is linked to several diseases, including cancer. The development of MAGL inhibitors has been greatly limited by the side effects associated with the prolonged MAGL inactivation. Importantly, it could be preferable to use reversible MAGL inhibitors in vivo, but nowadays only few reversible compounds have been developed. In the present study, structural optimization of a previously developed class of MAGL inhibitors led to the identification of compound 23, which proved to be a very potent reversible MAGL inhibitor (IC 50 = 80 nM), selective for MAGL over the other main components of the endocannabinoid system, endowed of a promising antiproliferative activity in a series of cancer cell lines and able to block MAGL both in cell-based as well as in vivo assays
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
Stereoselective Synthesis of a Monocyclic Peloruside A Analogue
No full textThe stereoselective synthesis of the monocyclic peloruside A analogue 4 has been achieved, following a new efficient approach for the introduction of the side chain, involving a late-stage addition of vinyl lithium species 7a to aldehyde 8. Further key steps are a highly diastereoselective allyltitanation reaction and a RCM-based macrocyclization
Stereoselective Synthesis of a Monocyclic Peloruside A Analogue
No full textThe stereoselective synthesis of the monocyclic peloruside A analogue 4 has been achieved, following a new efficient approach for the introduction of the side chain, involving a late-stage addition of vinyl lithium species 7a to aldehyde 8. Further key steps are a highly diastereoselective allyltitanation reaction and a RCM-based macrocyclization
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
Stereoselective Synthesis of 12,13-Cyclopropyl-Epothilone B and Side-Chain-Modified Variants
No full textA general strategy has been devised for the stereoselective synthesis of 12,13-cyclopropyl-epothilone B and side-chain-modified variants thereof, which relies on late stage introduction of the heterocycle through Wittig olefination of ketone 14. Formation of the macrocycle was achieved through RCM-based ring closure and introduction of the cyclopropane moiety involved a highly selective Charette cyclopropanation of allylic alcohol 7
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