1,721,051 research outputs found
Synthesis of novel 1,2,4-oxadiazole topsentin analogs with antitumor activity
Get PDFSynthesis of novel 1,2,4-oxadiazole topsentin analogs
with antitumor activit
Eight-membered heterocycles with two heteroatoms in a 1,2-relationship of interest in medicinal chemistry
No full textThis chapter treats 1,2-diheterocines, eight membered heterocyclic systems with two
heteroatoms, N, O and S, in an 1,2 relationship, exhibiting biological properties and
exhaustively covers the literature from 2007 to the end of November 2019.
In this period of time 1,2-diazocine, 1,2-oxazocine, 1,2-dioxocin and 1,5-dithiocin
ring systems had derivatives exhibiting pharmacological activities. No articles on biological
properties have been reported for 1,2-thiazocines and 1,2-oxathiocins.
Besides uncondensed derivatives, 1,2-diheterocines fused with five-, six-, and sevenmembered
carbocycles or heterocycles have been reviewed, as well as bridged
1,2-diheterocines
New Tripentone Analogs with Antiproliferative Activity
Get PDFTripentones represent an interesting class of compounds due to their significant cytotoxicity against different human tumor cells in the submicro-nanomolar range. New tripentone analogs, in which a pyridine moiety replaces the thiophene ring originating the fused azaindole system endowed with anticancer activity viz 8H-thieno[2,3-b]pyrrolizinones, were efficiently synthesized in four steps with fair overall yields (34–57%). All tripentone derivatives were tested in the range of 0.1–100 μM for cytotoxicity against two human tumor cell lines, HCT-116 (human colorectal carcinoma) and MCF-7 (human breast cancer). The most active derivative, with GI50 values of 4.25 µM and 20.73 µM for HCT-116 and MCF-7 cells, respectively, did not affect the viability of Caco-2 differentiated in normal intestinal-like cells, suggesting tumor cells as the main target of its cytotoxic action. The same compound was further investigated in order to study its mode of action. Results showed that it did not exert necrotic effects, while induced a clear shift of viable cells towards early apoptosis. Flow cytometric analysis demonstrated that this compound caused cell cycle alteration, inhibiting its progression in S and G2/M phases
An overview of recent molecular dynamics applications as medicinal chemistry tools for the undruggable site challenge
Get PDFMolecular Dynamics (MD) has become increasingly popular due to the development of hardware and software solutions
and improvement in algorithms, that allowed researchers to scale up calculations in order to speed up them. MD
simulations are usually used to address protein folding issues or protein-ligand complex stability through energy profile
analysis over time. In recent years, the development of new tools able to deeply explore Potential Energy Surface (PES)
allowed researchers to focus on the dynamic nature of binding recognition process and binding-induced protein
conformational change. Moreover, modern approaches have demonstrated to be effective and reliable in calculating some
kinetic and thermodynamic parameters behind the host-guest recognition process. Starting from all of these
considerations, several efforts have been made in order to integrate MD within the virtual screening process in drug
discovery. Knowledge retrieved from MD can be, in fact, exploited as a starting point to build pharmacophores or docking
constraints in the early stage of the screening campaign as well as to define key features, in order to unravel hidden
binding modes and help the optimisation of the molecular structure of a lead compound. Based on these outcomes,
researchers are nowadays using MD as an invaluable tool to discover and target previously considered undruggable
binding sites, including protein-protein interactions and allosteric sites on protein surface. As a matter of fact, the use of
MD has been recognised as vital in the discovery of selective protein-protein interaction modulators. The use of a dynamic
overview on how the host-guest recognition occurs and of the relative conformational modifications induced, allow
researchers to optimise small molecules and small peptides capable to tightly interact within the cleft between the two
proteins.
In this review we point to present the most recent applications of MD as integrated tool to be used in the rational design
of small molecules or small peptides able to modulate undruggable targets, such as allosteric sites and protein-protein
interactions
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
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