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SYNTHESIS AND CYTOTOXICITY OF DNA-INTERACTIVE PYRROLO[2,1-C][1,4]BENZODIAZEPINONE HETEROCYCLIC-ANALOGS
No full textThe pyrrolo[2,1-C][1,4]benzodizepines (PBDs) are a family of sequence-selective DNA-binding anti tumor antibiotics that bind exclusively to the exocyclic N2 of guanine in the minor groove of DNA. Footprinting-type studies have shown that the adduct span 3 base-pairs with a rank order of preference for 5'-Pu-G-Pu>5'->Pu-G-Py or 5'-Py-G-Pu>5'-Py-G-Py sequences. In a project aimed to design new analogues lacking both cardiotoxicity and tissue necrosis, we have substituted theA benzene ring of the PBD skeleton with different heterocycle nucleus such as substituted pyrazoles, pyridine and pyrimidine. The rationale behind the synthesis of the heterocyclic analogues reported here has been to design molecules with the following features:i)a possibly higher binding affinity and modified sequence selectivity for the DNAminor groove, due to the potential new hydrogen bonds that might occur between the A-ring atoms and DNA bases;ii)a reduced cardiotoxicity due to the impossibility of C9-quinone formation as occurs with anthramycin. The synthesized compounds were evaluated for cytotoxicity by growth inhibition studies in L1210 murine leukemia and its L1210/L-PAM sublime cells resistant to melphalan (L-PAM) and LoVo human coloncarcinoma and its sublime (LoVo/DX) resistant to Doxorubicin(DX). Among the most cytotoxic compounds containing the pyrazole ring it is interesting to note that:1)substitution at N7 increases cytotoxicity with respect to the N6 substituted compounds in L1210 and L1210/L-PAM cell lines;2)the N7 benzyl or N7 substituted benzyl compounds are similar or superior to N7 methyl or ethyl substituted compounds in terms of cytotoxicity; 3)with the same substituent at N6 replacement of the C8 methyl group with a carboxy methyl ester does not increase cytotoxicity.4)in the L1210 cell line, the introduction of a sterically demanding substituent at C8leads to a decrease in citotoxicity compared to the C8-methyl compound
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
Preparation of distamycin acryloyl derivatives as antitumor agents
No full textCompounds which are acryloyl substituted distamycin derivatives have been synthesized as antitumor agents
Synthesis and growth inhibition activity of alpha-bromoacrylic heterocyclic and benzoheterocyclic derivatives of distamycin A modified on the amidino moiety
No full textThe design, synthesis and in vitro activities of novel alpha-bromoacryloyl pyrazole, imidazole and benzoheterocyclic derivatives of distamycin A, in which the amidino moiety has been replaced by moieties of different physico-chemical features are described, and the structure-activity relationships are discussed. In spite of the relevance of these modifications on the distamycin frame, these derivatives showed significant growth inhibitory activity against mouse leukemia L1210 cells. Therefore, the presence of the amidino moiety, and in general of a basic moiety, is not an absolute requirement for biological activity of alpha-bromoacrylic derivatives of distamycin
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