1,720,986 research outputs found
Investigation about the mechanism of action of new antiproliferative compounds
Full text linkMy research activity deals with the evaluation of the mechanism of action of new compounds with potential anticancer action. I studied molecules that demonstrated their antiproliferative activity without or after UV-A irradiation (photochemotherapics).
EVALUATION OF NEW POTENTIAL ANTICANCER AGENTS:
Quinoxalines and structure-related quinoxalinones represent an important class of molecules with antiproliferative activity. A series of new isoindolo[2,1-a]quinoxalin-6-ones derivatives was synthesized in Palermo University (Dipartimento Farmaco-Chimico, Tossicologico and Biologico) and the mechanism of action of the most active compound, ISQ3 , was evaluated. In fact, ISQ3 showed a very interesting antineoplastic activity reaching nanomolar IC50 values in many human tumor cell lines.
Cell death mode was checked through flow cytometry, searching for such typical apoptotic features as the loss of plasmatic membrane asymmetry after the exposure of phospholipids. This translocation is needed for the recognition of apoptotic cells by macrophages. Potential modifications in cell cycle were examined after the treatment with ISQ3. Then, the involvement of mitochondria in cell death was studied searching signals of a possible mitochondrial dysfunction. We started from the compound characteristics to find potential cellular targets.
EVALUATION OF NEW POTENTIAL PHOTOCHEMOTHERAPIC AGENTS:
PUVA therapy combines the action of psoralens with UV-A radiation for the cure of dermatological diseases with a hyperproliferative/ autoimmune character, for instance psoriasis, vitiligo and mycosis fungoides. This treatment presents some long-term adverse effects, such as mutagenesis and increased onset of cutaneous tumors, as a consequence of the formation of cross-links with DNA. Thus, there is an enhanced research of new derivatives with the same potency but devoid of the capability to induce DNA cross-links. In particular, the photochemical and photobiological properties of new angelicin, or angular furocoumarin, analogues, in which both oxygens were substituted with other heteroatoms, were studied. In fact, the synthesis of thiopyrano[2,3-e]indol-2-ones (L series) and pyrrolo[3,4-h]quinolin-2-ones (BV series) was conducted in Palermo University because the incapability of inducing DNA cross-links for geometry problems was supposed. Thus, DNA binding and photodamage properties, antiproliferative and phototoxic activity, the mechanism of cell death were evaluated for the most active compounds
Isolation and structure elucidation of the main UV-A photoproducts of vandetanib
No full textExposure of aqueous solutions of the antitumor drug vandetanib to UV-A light results in the photochemical degradation. Two main photodegradation products were identified by HPLC-MS analysis and their structures were elucidated, after their isolation by HPLC, on the basis of LC-MS and NMR spectra. The photoproducts derived from a simple debromination (N-(2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4 yl)methoxy)quinazolin-4-amine, FP3) or from the loss of the bromide atom followed by the solvent addition (N-(4-hydroxy-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4 yl)methoxy)quinazolin-4-amine, FP2). At our knowledge this is the first report about the photodegradation of vandetanib. © 2013 Elsevier B.V
Furoquinazolines as furocoumarin analogs: can we improve solubility without impairing biological activity?
No full textFurocoumarins are well known photodynamic agents able to intercalate into DNA and to further react with the pyrimidine DNA bases under UVA irradiation, thereby blocking DNA processing and functions. Hence, psoralens (linear furocoumarins), such as 8-methoxypsoralen (8-MOP) or 5-methoxypsoralen (5-MOP), are commonly used in the photochemotherapy of psoriasis and related skin diseases. The ability of psoralens to form diadducts with DNA bases gives rise to crosslinking between DNA chains. For this reason the photochemotherapy with psoralens has some side effects such as skin phototoxicity and risk of skin cancer. In contrast to psoralens, angelicins (linear furocoumarins) generally show lower mutagenic activity. In order to reduce toxic effects of parent compounds, many isomers and/or isosters have been studied, but they all suffer from solubility problems in aqueous media, thus limiting in vitro studies and future therapeutic applications.
To investigate if the solubility could be improved without affecting the reactivity of the parent compound toward DNA, new furoquinazoline compounds have been designed.
The furoquinazoline nucleus maintains two key features of furocoumarins: a tricyclic planar system, required for DNA intercalation, and a non aromatic double bond, which could undergo photocycloaddition with DNA bases.
The title compounds have been synthesized condensing the furan ring on the N-protected aminophenol, then cyclizing the quinazoline moiety with HTMA/K3Fe(CN)6 method. Both angular and linear isomers have been obtained from the same aminobenzofuran intermediate, thus they have been separated by flash-chromatography.
To detect the kind of damage induced by these new compounds, linear flow dichroism measurements and DNA-photobinding studies have been performed. Moreover, reactive oxygen species formation and photooxidation of lipids and proteins were studied to determine the mechanism underlying phototoxicity demonstrated in Jurkat and NCTC-2544 cell lines specially by the linear derivative
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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