323,853 research outputs found
Recent highlights in the synthesis of highly functionalized pyrimidines
No full textThe pyrimidine scaffold represents an important pharmacophore endowed with a wide range of pharmacological activities according to the specific decoration of the heterocycle. This perspective article will briefly outline the most interesting approaches recently reported for the synthesis of highly functionalized pyrimidine derivatives
Héctor Schenone and the Musem Fernández Blanco. The academic construction of a collection
No full textEl Museo de Arte Hispanoamericano Isaac Fernández Blanco, creado en el siglo XIX, se convirtió en la institución más prestigiosa de la Argentina dedicada al arte colonial.Construir la identidad del museo demandó la suma de acciones políticas, intelectuales y administrativas. El momento cúlmine fue en los años ´60, cuando el profesor Héctor Schenone, el principal referente en historia del arte colonial de la Argentina, se convirtió en su director.Este artículo se propone mostrar el fortalecimiento de la institución y analizar los aspectos más importantes de la gestión del profesor Schenone quien, como académico, funcionario, historiador del arte y coleccionista, decidió reformular y otorgar nuevos significados al patrimonio del museo.The Museum of Hispanic American Art “Isaac Fernández Blanco”, which was created in the 19th century as a private museum of Argentine history and of American and European handcrafts, developed in the most prestigious institution dedicated to colonial art.The identity of the museum demanded a sum of political, intellectual and administrative actions for years. The most significant ones were its transfer, in 1943, to its local site in Suipacha 1422, and its later merge with the Colonial Museum. In the 60´s a new event contributed towards its new identity: Prof. Héctor Schenone, main referent of Colonial Art History in Argentina, was appointed director of the museum.This article aims to show the ideological motives that enabled these changes within the insitutution, as well as to analyze the most relevant issues of Prof. Schenone´s performance who, as an academic professor, decided to reformulate and bring new meanings to the museum heritage, from the multiple points of view he owned as public official, art historian and specialized collector
Allosteric Inhibitors of Bcr-Abl: Towards Novel Myristate-Pocket Binders
No full textAmong the currently available options for the treatment of chronic myeloid leukemia (CML), ATP-competitive tyrosine kinases inhibitors (Gleevec®, Dasatinib® and Nilotinib®) represent one of the most promising therapeutic approaches developed in the last 10-15 years. However, the initial enthusiasm generated by the high response rate to these drugs has been dampened by the development of resistance. The T315I mutation at the gatekeeper residue is very frequent in advanced phases of the disease and is one of the main causes of resistance, disrupting important contact points between the inhibitors and the enzyme. Different strategies have been implemented to overcome this resistance, such as the recent development of more selective non-ATP competitive inhibitors targeting sites outside the ATP-binding cleft. Some of these allosteric inhibitors alter the kinase conformation, while others directly compete with the protein substrates. Another interesting family of allosteric inhibitors is represented by those compounds targeting the myristate-pocket of Bcr-Abl (myristate-pocket binders). The binding of these inhibitors blocks the Bcr-Abl kinase in the inactive conformation and provides an advantage in overcoming drug resistance due to kinase mutations. This review reports the last findings in the development of novel myristate-pocket binders of Bcr-Abl as promising anti-leukemia agents
Expert integrated system for production and logistic management in a small-medium enterprise
No full textProposing a new framework for lean warehousing: first experimental validations
No full textLean principles have been increasingly adopted in manufacturing over the last decades and they have just recently spread their applicability to supply chains. In such a context, lean warehousing plays a significant role in order to achieve lower costs of logistics operations and increase flexibility and efficiency in pull supply chains driven by customer demand. However, both academic and professional literature is still poor and lacks structured methodologies and case studies integrating different lean techniques to optimize warehouse processes. This paper proposes a novel lean warehousing framework combining three well-known lean tools and presents the first outcomes of its validation campaign. In particular, it discusses the framework application to a raw material and component warehouse of an international company in the automotive sector. Results show that time savings up to
36% might be achieved in receiving, put away, and picking operations, bringing significant economic benefits in terms of labour, service level, and warehouse space. This study provides researchers with new opportunities for fostering continuous improvement in warehouse operations, while practitioners might benefit from it as a basis for evaluating and re-engineering warehouse processes towards lean principles. Future research will further validate and progress the lean warehousing framework
Using insights into pim1 structure to design new anticancer drugs
No full textHuman Pim1 (proviral integration site for Moloney murine leukemia virus) kinase is a 313-amino acid serine-threonine kinase that possesses several biological functions in cell survival, proliferation and differentiation, and its overexpression has been observed in a number of human cancers. Indeed, this kinase is a proto-oncogene that has been implicated in early transformation and tumor progression, especially in hematopoietic malignancies and prostate carcinoma where it is a marker of a poor prognosis. For these reasons, Pim1 is emerging as an important target in drug discovery, and many Pim1 inhibitors have been reported in the last three years. The challenge of this research is to obtain compounds that specifically inhibit only Pim1 and not Pim2 and Pim3, the other members of the Pim family, with the aim of providing selective inhibitors as potential therapeutic agents and also of studying the different roles of the three enzymes. In this review Pim1 functions and Pim1 role in human cancer are summarized, but the primary focus of the article is on the Pim1 three-dimensional structure that was deeply analyzed by a detailed inspection of the available crystallographic data and all complexes of small molecule inhibitors reported in the literature to this point. Finally, the use of molecular modeling techniques for the identification and optimization of Pim1 inhibitors is extensively discussed. This data collection, which to the best of our knowledge was not previously reviewed in such detail, could offer a useful tool for medicinal chemists working in the field of small molecule kinase inhibitors
Correction to: Daytime sleepiness and sleep quality in Charcot–Marie–Tooth disease (Journal of Neurology, (2023), 270, 11, (5561-5568), 10.1007/s00415-023-11911-y)
No full textThe article Daytime sleepiness and sleep quality in Charcot–Marie–Tooth disease, written by Marta Bellofatto, Luca Gentile, Alessandro Bertini, Irene Tramacere, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Lucio Santoro, Tiziana Cavallaro, Marina Grandis, Stefano C. Previtali, Marina Scarlato, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Flavio Villani, Eleonora Cavalca, Paola Saveri, Aldo Quattrone, Paola Valentino, Stefano Tozza, Massimo Russo, Anna Mazzeo, Giuseppe Vita, Sylvie Piacentini, Giuseppe Didato, Chiara Pisciotta, Davide Pareyson and for the Italian C. M. T. Network was originally published electronically on the publisher’s internet portal on 04 August 2023 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 19 August 2023 to © The Authors 2023 and this article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit. The original article has been corrected
Guanylated Diamines, Triamines, and Polyamines: Chemistry and biological properties
No full textNaturally occurring polyamines (PAs) play a pivotal role in the life of all organisms from bacteria to man. The human PAs putrescine, spermidine, and spermine are fundamental for cell viability, having a multitude of in vivo functions, and their study is an expanding field of research. The polycationic nature of these polyamines is important for their biological activities and for their in vivo interaction with macromolecules such as enzymes or the polyanionic nucleic acids. Several reviews have been reported so far on the chemistry, synthesis, and biological properties of polyamines.
However, a particular class of polyamines, namely, the guanylated polyamines, attracted the attention of many chemists and biologists in the last decades. A guanylated polyamine is a polyamine with one or more of its amino moieties as part of a guanidine function. These compounds can be sometimes referred to as polyaminoalkylguanidines. Replacement of an amino group in a biologically active polyamine compound by the strongly basic guanidinium results often in a significant increase of its potency and/or selectivity. In fact, the guanidine group is a common structural key element in a variety of natural and synthetic compounds, which show interesting biological properties or chemical behavior and have therefore found important applications in medicinal, bioorganic, supramolecular chemistry, and, most recently, asymmetric synthesis. A guanidinium group is commonly used by proteins and enzymes to recognize and bind anions through ion pairing and hydrogen bonding. The specific patterns of hydrogen bonding recognition together with the high basicity (pKa ≈ 13.5) makes the guanidium group able to play several key roles in recognition, electrophilic catalysis, and biological activity in many enzymes. As a consequence, guanylated polyamines may possess biochemical and biophysical properties amplified with respect to their parent polyamines. Moreover, being strictly related to natural bioamines and amino acids, the guanylated polyamines often have high solubility in water and bioavailability, which makes them excellent drugs or lead compounds. Guanylated polyamines (in particular guanylated diamines and triamines) play important roles in biological processes and might be produced directly by plants, animals, and humans. However, despite their simple chemical structures, these compounds showed difficulties from a synthetic point of view, mostly due to the nature of guanidine moiety, which makes these compounds highly polar and hard to handle and to purify. In addition, the presence of two or more nitrogens or guanidine moieties represents an additional issue: for instance, the regioselctive guanylation of polyamines still represents a big challenge for chemists. Different synthetic methodologies have been reported to overcome these issues such as the shrewd use of a protecting group strategy or the use of solid-phase synthesis. Moreover, possessing these compounds different reactive moieties, side reactions sometimes constitute a problem.
This review will cover systematically the preparation methodologies and chemical properties of guanylated diamines, triamines, and, more generally, polyamines. Finally, a description of their most important biological properties will be reported
Evaluation of the ocular surface after disinfection with povidone-iodine for cataract surgery.
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