1,720,969 research outputs found
Development of a reliable synthetic scheme to isolate 2-hydroxy-2-benzodioxanylethoxy benzamides for the obtainment of fluorescent probles
No full textAiming at fighting antimicrobial resistance when acting on an innovative target, we developed a class of FtsZ inhibitors as promising new antimicrobials, which are structurally benzodioxane-benzamides. While characterizing the mechanism of action of this class of compounds, the need of a FtsZ fluorescent ligand to determine several biochemical data, such as confocal microscopy images of protein-ligand co-localization, arose. Therefore, starting from the structure of our strongest compound, which is able to interact and perturb both S. aureus and E. coli FtsZs, we decided to introduce an -OH group as an anchoring point for the preparation of both prodrugs and fluorescent probes, by inserting a proper dye (compound I-OH). This compound required the design of an ad hoc synthetic pathway, able to separate the two diastereomeric threo and erythro couples. A common intermediate of this synthesis is the epoxydic derivative (Scaffold A), obtained as a mixture of the two diastereomeric pairs, and soon chromatographied achieving the isolated diastereoisomers, which parallelly underwent ring opening, yielding to the final desired compounds (I-OH threo and I-OH erythro). After their isolation, each couple of enantiomers were linked to a proper fluorescent dye through a suitable spacer (Figure 1). With this work, we developed a synthetic scheme applicable to all the benzodioxane-benzamides FtsZ inhibitors, regardless the substitution of the benzodioxane moiety, to obtain hydroxylated derivatives
Study of isosteric substitution of the 1,4-benzodioxane oxygen atoms in benzamides FtsZ inhibitors
Full text linkMulti-Drug Resistant bacterial infections are predicted to cause more than 10 million deaths each year by 2050. Among several factors, the development of this global health-threatening problem is primary caused by the lack of new antibiotics being developed.
In this context, targeting the cell division system can be the strategy to bypass antibiotic resistance. In particular, FtsZ is an optimal target: is a crucial protein for the bacterial division system, it is highly conserved between bacteria and mycobacteria and shares only less than 20% of sequence with its human functional homologue (β-tubulin).
In the last year we developed a class of potent FtsZ inhibitors with an 1,4-benzodioxane-benzamide structure characterized by high activity (MIC < 1 μg/mL vs both MSSA and MRSA). The oxygen atoms of the benzodioxane ring were successively replaced with bioisosteric atoms like Nitrogen, Sulfur and Carbon. Here we report the synthesis and the biological results of these derivatives.
We demonstrated the importance of the Oxygen in 1- position in the 1,4-benzodioxane moiety in the maintaining of the antimicrobial activity. Conversely, the nature of the heteroatom at 4- position can differently modulate the antimicrobial activity of the derivative
(3-Methylene-2,3-dihydronaphtho[2,3-b][1,4]dioxin-2-yl)methanol
Full text link(3-Methylene-2,3-dihydronaphtho[2,3-b][1,4]dioxin-2-yl)methanol was unexpectedly achieved as the main reaction product while applying a standard Johnson–Corey–Chaykovsky procedure to the 2,3-dihydronaphtho[2,3-b][1,4]dioxine-2-carbaldehyde, aiming at obtaining the corresponding epoxide. The structure of the recovered compound was confirmed through NMR and HRMS, the melting point was measured by DSC, and the organic purity was assessed using HPLC. We hypothesized the possible mechanism for the obtainment of this side product, which should involve the opening of the dioxane ring soon after the nucleophilic attack of the ylide to the carbonyl function. The consequent transfer of the negative charge allows the achievement of the phenolate function. The tautomer further rearranges, forming the unstable oxirane, which opening is favored by the acidic phenolic function, thus closing into the more stable six-membered ring compound. We confirmed the hypothesized reaction mechanism by applying the same reaction conditions while starting from the corresponding methyl ketone. This undesired compound, easily and quantitatively obtained by standard Johnson–Corey–Chaykovsky conditions, could pave the way to a new methodology for the obtainment of 2,3-disubstituted 1,4-naphthodioxanes, further derivatizable
How reaction conditions may influence the regioselectivity in the synthesis of 2,3-dihydro-1,4-benzoxathiine derivatives
Full text linkThe exploration of different reaction conditions aiming to obtain both 2,3-dihydro-1,4-benzoxathiine-2-yl derivatives and 2,3-dihydro-1,4-benzoxathiine-3-yl ones is reported. The treatment of 1,2-mercaptophenol with an organic base and a specific 2-bromo acrylate results in a solvent- and substrate-dependent exclusive solvation of O- and S-anions, thus managing the regioselectivity
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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