1,720,988 research outputs found
Synthesis, characterization and antiproliferative activity of amino- and DMSO complexes of platinum(II) containing L-carnitine
No full textL-Carnitine, a biomolecule able to cross the blood-brain barrier exploiting specific transporters, behaves as mono or bidentate anionic ligand for Pt(II) in the new amino complexes cis-[Pt(L-carnitine-O)2(NH3)2](BF4)2 (1), cis-[PtCl(L-carnitina-O)(NH3)2]BF4 (2), [Pt(L-carnitine-O,O’)(1,2-DACH)]BF4 (3), [Pt(L-carnitine-O)2(1,2-DACH)](BF4)2 (4), and [PtCl(L-carnitine-O)(1,2-DACH)](BF4) (5). Four complexes with DMSO have been also prepared and characterized: the synthetic intermediate [Pt(CO3)(DMSO)2] (6), [Pt(L-carnitine-O,O’)(DMSO)2]BF4 (7), cis-[Pt(L-carnitine-O)2(DMSO)2](BF4)2 (8) and cis-[PtCl(L-carnitine-O)(DMSO)2]BF4, (9).
The antiproliferative activity of three representative complexes 1, 5 and 7 has been assayed against three human cancer cell lines A2780, K562 and SKOV3, and it was found comparable to that of the parent active compounds cis-[PtCl2(1,2-DACH)] and cisplatin
AGHLDDLPGALSAL: A hemoglobin fragment potentially competing with albumin to bind transition metal ions
No full textProtein degradation leads to the formation of endogenous peptides, the biological activity of which is most often unknown. The peptide AGHLDDLPGALSAL, recently isolated from mouse brain homogenates, has been recognized as a fragment of the α-chain of hemoglobin. AGHLDDLPGALSAL has the ability of inhibiting the peripheral hyperalgesic inflammatory responses through the indirect activation of the μ-opioid receptors. A peculiarity of AGHLDDLPGALSAL is the presence, at its N-terminus of a strong binding site for divalent transition metal ions, similar to that characterizing the human albumin and called “ATCUN motif”. The consequential metal binding ability of AGHLDDLPGALSAL can be connected to its biological activity. For this reason, we decided to investigate the coordination properties of AGHLDDLPGALSAL towards Cu(II), Ni(II) and Zn(II) ions, reported here for the first time. The results confirm that AGHLDDLPGALSAL is a strong ligand for those metals: it can even compete with albumin under suitable conditions. In vitro assays on the inhibition of Cu(II) toxicity towards different cell lines confirmed that the binding ability of AGHLDDLPGALSAL can imply relevant biological consequences
Studies of C-terminal naphthoquinone dipeptides as 20S proteasome inhibitors
No full textThe ubiquitin proteasome pathway is crucial in regulating many processes in the cell. Modulation of proteasome activities has emerged as a powerful strategy for potential therapies against much important pathologies. In particular, specific inhibitors may represent a useful tool for the treatment of tumors. Here, we report studies of a new series of peptide-based analogues bearing a naphthoquinone pharmacophoric unit at the C-terminal position. Some derivatives showed inhibition in the μM range of the post-acidic-like and chymotrypsin-like active sites of the proteasome
Rutin-containing cyclodextrin nanosystems: a possible strategy for dietary supplementation in diabetics
No full textThe flavonoid rutin is an active ingredient with multiple health benefits featuring antioxidant, anti-inflammatory, cardiovascular, neuroprotective, anti-diabetic and anti-tumor activity, unfortunately characterized by physico-chemical instability and poor solubility in aqueous environment. The present study investigates the use of nanosystems for the delivery of rutin through oral administration for a possible dietary supplementation. In this view, rutin-containing cyclodextrins and rutin-in-cyclodextrin-in-liposomes (R-CL) have been studied. R-CL, obtained by the “thin film hydration” method, were initially homogeneous in size, but increased in the average diameter over time. R-CL showed greater encapsulation efficiency and stability of rutin over time compared to cyclodextrin complexes. R-CL were stable in term of rutin content and physically within 30 days of storage in a cool environment, showing no phase separation phenomena. The dialysis study through a Wistar rat small intestine fragment, demonstrated an increasing release of rutin from R-CL, reaching the plateau around the sixth hour. The use of a gastrointestinal fluid simulator within the selected biological fragment, led to a more linear and gradual release profile over time, still obtaining a complete release of the drug around the sixth hour. The in vitro experiments on HepG2 cells evidenced no cytotoxic effect for both R-CL and cyclodextrin-complex and a strong and significant increase in glucose uptake levels promoted by R-CL with respect to untreated cells, as well as to the other formulations. The data suggest that the formulation strategy based on the vesicular cyclodextrin system improves the biological effect of rutin on cells. However, further studies will be necessary to confirm the activity of rutin as food supplementation
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
Naphthoquinone amino acid derivatives, synthesis and biological activity as proteasome inhibitors
No full textThe ubiquitin-proteasome system has been largely investigated for its key role in protein degradation mechanisms that regulate both apoptosis and cell division. Because of their antitumour activity, different classes of proteasome inhibitors have been identified to date. Some of these compounds are currently employed in the clinical treatment of several types of cancer among which multiple myeloma. Here, we describe the design, chemistry, biological activity and modelling studies of a large series of amino acid derivatives linked to a naphthoquinone pharmacophoric group through variable spacers. Some analogues showed interesting inhibitory potency for the β1 and β5 subunits of the proteasome with IC50 values in the sub-µm range
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
Synthesis and Biological Activity of Peptide α-Ketoamide Derivatives as Proteasome Inhibitors
No full textProteasome activity affects cell cycle progression as well as the immune response, and it is largely recognized as an attractive pharmacological target for potential therapies against several diseases. Herein we present the synthesis of a series of pseudodi/tripeptides bearing at the C-terminal position different α-ketoamide moieties as pharmacophoric units for the interaction with the catalytic threonine residue that sustains the proteolytic action of the proteasome. Among these, we identified the 1-naphthyl derivative 13c as a potent and selective inhibitor of the β5 subunit of the 20S proteasome, exhibiting nanomolar potency in vitro (β5 IC50 = 7 nM, β1 IC50 = 60 μM, β2 IC50 > 100 μM). Furthermore, it significantly inhibited proliferation and induced apoptosis of the human colorectal carcinoma cell line HCT116
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
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