1,720,956 research outputs found
Synthesis of IR-analogue of cyclopamine and enzymatic enantioselective synthesis of (S)-norcoclaurine
No full textThe huge biosynthetic potential of plants as a renewable source of fine chemicals and pharmaceuticals has long been recognized. Identification of biologically active compounds from plants and improvement of the isolation methods are of great interest for their therapeutic applications. Moreover, they are a huge source of inspiration for the design of new active compounds, not only for their structure, carrying the features responsible for drug’s biological activity, but also for the biosynthetic pathways that Nature has established for them, often a suggestion for an easier synthetic access to the targeted molecule. Therefore, the future demands for pharmaceuticals is dependent on a detailed understanding of the biologically active compounds, of their biosynthetic pathways as well as the complex mechanisms regulating the development of diseases. Thus in both sections of this work two biologically active compounds and their therapeutic properties are discussed in relation to their methods of synthesis.
The first part of this work deals with the synthesis of a potential inhibitor of the hedgehog signaling pathway, a key regulator of multiple developmental processes of embryogenesis as well as in adult tissue maintenance and repair. Since its aberrant activation has been linked to the development of severe malignancies, the hedgehog signaling inhibitors has emerged as a valuable tool for cancer treatment. Several modulators have been reported so far, including cyclopamine, the first known inhibitor identified in 1968. Since its discovery, only in 2009 the first synthetic route to cyclopamine was established by Giannis et al. using a biomimetic and diastereoselective approach. This flexible synthetic strategy provides access to several structural modifications leading to multiple potential analogues of cyclopamine that do not exist in nature. Exploiting this route, in order to have new insights into the biological activity of the natural compound, the first synthetic analogue of cyclopamine was designed and partially synthesized.
In the second part of this work the catalytic activity of (S)-norcoclaurine synthase was investigated and used to set up a method for an easy access to (S)-norcoclaurine, the first common intermediate of all benzylisoquinoline alkaloids. Recently (S)-norcoclaurine gained a widespread interest in both organic and medicinal chemistry for its well recognized rich pharmacological potential in the treatment of several diseases. So far, several synthetic strategies have been employed based on asymmetric catalytic approaches involving the use of a chiral metal catalyst. Even though these synthetic routes are highly efficient and guarantee a very good enantioselectivity, they entail extensive use of organic solvents and metal catalysts. In order to develop a clean and green synthetic process towards (S)-norcoclaurine without using organic solvents and metal catalysts, an efficient one pot-two steps synthesis was set up, starting from tyrosine and dopamine in the presence of (S)-norcoclaurine synthase providing the first attempt to exploit the potential of a “Pictet-Spengler” enzyme in the direct synthesis of chiral benzylisoquinolines
Chromane derivatives of small aromatic molecules: Chemoenzymatic synthesis and growth inhibitory activity on human tumor cell line LoVo WT
No full textAromatic substrates tyrosol (p-hydroxyphenylethanol) and 2,6-dihydroxynaphthalene (2,6-DHN) were converted into chromane derivatives by means of chemoenzymatic reactions catalyzed by the aromatic prenyltransferase of bacterial origin NovQ, using dimethylallyl bromide as allylic substrate instead of the natural isoprenyl pyrophosphate substrate. Stereoselective prenylation occurred in o-position with respect to the phenol hydroxyl in both compounds. Prenylated derivatives were readily converted into chromane products via a selective 6-endo-trig cyclization involving the oxygen atom from the phenol moiety and the double bond of the prenyl substituent, a process catalyzed by FeCl(3). These findings set up the basis of a most convenient two-step, one-pot process which allows for easy recovery of the chromane products in high yields. The chromane derivatives thus obtained were tested for cytotoxicity and pro-apoptotic activity using LoVo WT cells, a line of human colon adenocarcinoma. (C) 2009 Elsevier Ltd. All rights reserved
Chitosan enhances xanthone production in Hypericum perforatum subsp. angustifolium cell cultures
No full textHypericum perforatum is an important medicinal plant containing numerous biologically active compounds. The effect of chitosan elicitation on xanthone biosynthesis in calli and in cell suspension cultures of H. perforatum subsp. angustifolium was evaluated. Elicited cell cultures showed an increase in xanthone production and a simultaneous decrease in flavonoid production. Chitosan also induced the production of 1,7-dihydroxyxanthone (euxanthone) and cadensin G, which were not detected in either the calli nor the non-elicited cell cultures. 1,7-Dihydroxyxanthone was in part (21%) released in the culture medium
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
An enzymatic, stereoselective synthesis of (S)-norcoclaurine
No full textAn efficient, stereoselective, green synthesis of (S)-norcoclaurine (higenamine) has been developed using the recombinant (S)-norcoclaurine synthase (NCS) enzyme, starting from the cheap tyrosine and dopamine substrates in a one-pot, two step process. Key steps in the biotransformation consist of the oxidative decarboxylation of tyrosine by stoichiometric amounts of sodium hypochlorite in order to generate 4-hydroxyphenylacetadehyde, followed by the addition of enzyme and dopamine substrate in the presence of ascorbate, a necessary ingredient in order to avoid oxidation of the catechol moiety. Quantitative extraction of the product from an aqueous solution was achieved by adsorption onto active charcoal dispersed in the reaction mixture. The optimized process afforded enantiomerically pure (S)-norcoclaurine (93%) in a yield higher than 80% and allowed good recovery of the enzyme for recycling. The process thus developed represents the first example of a green Pictet-Spengler synthesis, which may pave the way to novel strategies in benzylisoquinoline alkaloid synthesis
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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