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11.
Dr. Maria L. Di Paolo Dr. Michael S. Christodoulou Dr. Alessandra M. Calogero Dr. Luca Pinzi Prof. Giulio Rastelli Prof. Daniele Passarella Prof. Graziella Cappelletti Prof. Lisa Dalla Via 《ChemMedChem》2019,14(18):1641-1652
A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (Ki) values in the sub-micromolar range and a good selectivity index (Ki MAO-A/Ki MAO-B>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity. 相似文献
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Dr. Simon Schramm Luca Agnetta Dr. Marcel Bermudez Hubert Gerwe Matthias Irmen Dr. Janine Holze Dr. Timo Littmann Prof. Gerhard Wolber Dr. Christian Tränkle Prof. Michael Decker 《ChemMedChem》2019,14(14):1349-1358
Recently, investigations of the complex mechanisms of allostery have led to a deeper understanding of G protein-coupled receptor (GPCR) activation and signaling processes. In this context, muscarinic acetylcholine receptors (mAChRs) are highly relevant due to their exemplary role in the study of allosteric modulation. In this work, we compare and discuss two sets of putatively dualsteric ligands, which were designed to connect carbachol to different types of allosteric ligands. We chose derivatives of TBPB [1-(1′-(2-tolyl)-1,4′-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one] as M1-selective putative bitopic ligands, and derivatives of benzyl quinolone carboxylic acid (BQCA) as an M1 positive allosteric modulator, varying the distance between the allosteric and orthosteric building blocks. Luciferase protein complementation assays demonstrated that linker length must be carefully chosen to yield either agonist or antagonist behavior. These findings may help to design biased signaling and/or different extents of efficacy. 相似文献
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Maria Rita Micheli Luca Berchicci Justin J.P. Jansen 《Creativity & Innovation Management》2020,29(2):198-208
The relevance of business model innovation (BMI) for strategic renewal and competitive advantage has been increasingly recognized by both strategy scholars and managers. In this paper, we explore how inter‐organizational networks and firms' proactiveness influence BMI. By examining Dutch design companies, we show that having a network of companies with different sizes has a positive effect on BMI. We also observe a positive effect of ties change. Finally, we show the importance of firms' proactiveness. Through the discussion of network elements and proactiveness as antecedents of BMI, we contribute to the business model and social network literature. 相似文献
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Luca Maria Chiesa Maria Nobile Federica Ceriani Francesco Arioli 《Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment》2018,35(7):1340-1355
Demand for honey is increasing, especially if it is organic and if its nutritional properties are linked to untreated environments in order to guarantee quality for health. Sources of contamination of honey can be divided into environmental and apicultural. Therefore, the distribution of persistent organic pollutants, pesticides and antibiotic residues from geographical areas with different contamination sources (high anthropic impact, intensive farming, husbandry and low anthropic impact) was investigated in order to confirm the potential transfer of xenobiotics into the supply chain and to give beekeepers tools for the selection of areas dedicated to organic production. The presence of polychlorinated biphenyls, polybrominated diphenyl ether and polycyclic aromatic hydrocarbons was confirmed, not only in proximity to highly urbanised centres, where the concentrations were higher, but in all environment contexts, confirming their ubiquity. No antibiotics or neonicotinoids were detected in 95 organic honeys, demonstrating the absence of apicultural treatments and consequently the good quality of honey of different areas. These results are important due to the undefined regulatory European situation on honey antibiotic limits. 相似文献
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Luca Pietrobon Lorenzo Fallarino Andreas Berger Andrey Chuvilin Flix Casanova Luis E. Hueso 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(47):6295-6301
Graphene has been predicted to develop a magnetic moment by proximity effect when placed on a ferromagnetic film, a promise that could open exciting possibilities in the fields of spintronics and magnetic data recording. In this work, the interplay between the magnetoresistance of graphene and the magnetization of an underlying ferromagnetic insulating film is studied in detail. A clear correlation between both magnitudes is observed but through a careful modeling of the magnetization and the weak localization measurements, that such correspondence can be explained by the effects of the magnetic stray fields arising from the ferromagnetic insulator is found. The results emphasize the complexity arising at the interface between magnetic and 2D materials. 相似文献
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