1,721,006 research outputs found
Drug design of tyrosinase inhibitors
No full textThis copper-containing enzyme catalyzes the rate-limiting step for the melanin skin pigment bioproduction. Tyrosinase inhibitors can be exploited as skin whitening agents and food preservatives, opening new scenarios in food, cosmetics, agriculture and medicine. Despite the availability of natural inhibitors (hydroquinone, α-arbutin, kojic acid, retinoids, azelaic acid, resveratrol, caftaric acid, valonea tannin, chrysosplenetin and phenylethyl resorcinol), several synthetic compounds were proposed to overcome side effects and to improve the efficacy of natural agents. This chapter will gather the recent advances about synthetic tyrosinase inhibitors from the MedChem perspective, providing new suggestions for the scaffold-based design of innovative compounds
Peptidyl 3-substituted 1-hydroxyureas as isosteric analogues of succinylhydroxamate MMP inhibitors
No full textTo evaluate N-hydroxyurea as zinc binding group in the design of MMP inhibitors, two peptidyl 1-hydroxyureas were prepared by N-hydroxycarbamoylation
of the diastereomeric dipeptides H-Leu-Phe-NHMe and H-D-Leu-Phe-NHMe. Peptidyl 1-hydroxyureas were more potent than
the parent peptides, but dramatically weaker (4e5 orders of magnitude) than the isosteric (R)-succinylhydroxamate analogue, which displays
IC50 in the range of nM vs MMP-1, -3, -7 and sub-nM vs MMP-2, -8, and -9. The peptidyl 1-hydroxyurea 1a attained an IC50 of 20 mM vs
MMP-9, and substantially approaches inhibition of known N-hydroxyureas based on aminoacids or peptides against other zinc metalloenzymes
and non-peptidic N-hydroxyureas against MMPs. Strong preference of the OeN1eC]O unit for the antiperiplanar amide bond conformation
seems to be the major limit for more effective zinc chelation. Methylation of a peptidyl 1-hydroxyurea at N3, to promote the synperiplanar
OeN1eC]O conformation required for zinc chelation and improve affinity, resulted in release of a methylimidazolidine-2,4-dione through
an undesired intramolecular reaction reminiscent of the Edman peptide degradation
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
Peptidyl 3-Substituted 1-Hydroxyureas as Isosteric Analogues of Succinylhydroxamate MMP Inhibitors
No full textTo evaluate N-hydroxyurea as zinc binding group in the design of MMP inhibitors, two peptidyl 1-hydroxyureas were prepared by N-hydroxycarbamoylation of the diastereomeric dipeptides H-Leu-Phe-NHMe and H-d-Leu-Phe-NHMe. Peptidyl 1-hydroxyureas were more potent than the parent peptides, but dramatically weaker (4-5 orders of magnitude) than the isosteric (R)-succinylhydroxamate analogue, which displays IC(50) in the range of nM vs MMP-1, -3, -7 and sub-nM vs MMP-2, -8, and -9. The peptidyl 1-hydroxyurea 1a attained an IC(50) of 20muM vs MMP-9, and substantially approaches inhibition of known N-hydroxyureas based on aminoacids or peptides against other zinc metalloenzymes and non-peptidic N-hydroxyureas against MMPs. Strong preference of the O-N1-CO unit for the antiperiplanar amide bond conformation seems to be the major limit for more effective zinc chelation. Methylation of a peptidyl 1-hydroxyurea at N3, to promote the synperiplanar O-N1-CO conformation required for zinc chelation and improve affinity, resulted in release of a methylimidazolidine-2,4-dione through an undesired intramolecular reaction reminiscent of the Edman peptide degradation
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
Natural products as a source of new anticancer chemotypes
No full textIntroduction: Exploring the chemical diversity and molecular mechanisms of natural products continues to be an important research area for identifying novel promising therapeutic approaches for fighting cancer. This is a complex disease and poses important challenges, which require not only targeted interventions to improve chemotherapy efficacy and tolerability, but also adjuvant strategies to counteract chemoresistance development and relapses. Areas covered: After a brief description of the recent literature on the anticancer potential of natural compounds, we searched for patents following the PRISMA guidelines, filtering the results published from 2019 onwards. In addition, some relevant publications from the overall scientific literature were also discussed. Expert opinion: This review comprehensively covers and analyzes the most recent advances on the anticancer mechanism of licensed natural compounds and their chemical optimization. Patentability of natural compounds was discussed according to the recent legislation in the U.S.A. and Europe
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