Search results for " DOC"
showing 10 items of 1281 documents
Discovery and structure-activity relationship studies of irreversible benzisothiazolinone-based inhibitors against Staphylococcus aureus sortase A tr…
2014
Gram-positive bacteria, in general, and staphylococci, in particular, are the widespread cause of nosocomial and community-acquired infections. The rapid evolvement of strains resistant to antibiotics currently in use is a serious challenge. Novel antimicrobial compounds have to be developed to fight these resistant bacteria, and sortase A, a bacterial cell wall enzyme, is a promising target for novel therapies. As a transpeptidase that covalently attaches various virulence factors to the cell surface, this enzyme plays a crucial role in the ability of bacteria to invade the host's tissues and to escape the immune response. In this study we have screened a small molecule library against rec…
Molecular topology applied to the discovery of 1-benzyl-2-(3-fluorophenyl)-4-hydroxy-3-(3-phenylpropanoyl)-2H-pyrrole-5-one as a non-ligand-binding-p…
2014
We report the discovery of 1-benzyl-2-(3- fluorophenyl)-4-hydroxy-3-(3-phenylpropanoyl)-2H-pyrrole- 5-one as a novel non-ligand binding pocket (non-LBP) antagonist of the androgen receptor (AR) through the application of molecular topology techniques. This compound, validated through time-resolved fluorescence resonance energy transfer and fluorescence polarization biological assays, provides the basis for lead optimization and structure−activity relationship analysis of a new series of non-LBP AR antagonists. Induced-fit docking and molecular dynamics studies have been performed to establish a consistent hypothesis for the interaction of the new active molecule on the AR surface. Refereed/…
Synthesis and Characterization of New Bivalent Agents as Melatonin- and Histamine H3-Ligands
2014
Melatonin is an endogenous molecule involved in many pathophysiological processes. In addition to the control of circadian rhythms, its antioxidant and neuroprotective properties have been widely described. Thus far, different bivalent compounds composed by a melatonin molecule linked to another neuroprotective agent were synthesized and tested for their ability to block neurodegenerative processes in vitro and in vivo. To identify a novel class of potential neuroprotective compounds, we prepared a series of bivalent ligands, in which a prototypic melatonergic ligand is connected to an imidazole-based H3 receptor antagonist through a flexible linker. Four imidazolyl-alkyloxy-anilinoethylami…
Antiproliferative properties and g-quadruplex-binding of symmetrical naphtho[1,2-b:8,7-b’]dithiophene derivatives
2021
Background: G-quadruplex (G4) forming sequences are recurrent in telomeres and promoter regions of several protooncogenes. In normal cells, the transient arrangements of DNA in G-tetrads may regulate replication, transcription, and translation processes. Tumors are characterized by uncontrolled cell growth and tissue invasiveness and some of them are possibly mediated by gene expression involving G-quadruplexes. The stabilization of G-quadruplex sequences with small molecules is considered a promising strategy in anticancer targeted therapy. Methods: Molecular virtual screening allowed us identifying novel symmetric bifunctionalized naphtho[1,2-b:8,7-b’]dithiophene ligands as interesting ca…
Synthesis, benzodiazepine receptor binding and molecular modelling of isochromeno[4,3-c]pyrazol-5(1H)-one derivatives
2012
Abstract A series of isochromeno[4,3-c]pyrazole-5(1H)-one derivatives 7b–h were prepared and tested at 10 μM for their ability to displace specific [3H]flunitrazepam from bovine brain membranes. The substitution pattern of the above derivatives was shown to influence the receptor affinity. The most active compound of the series was 7e, showing a 54% inhibition of [3H]flunitrazepam binding. Compounds 7a–d,i were compared with the known isomers chromeno[4,3-c]pyrazole-4(1H)-ones 14a–d,i, showing that the isochromene/chromene isomerism influences the activity.
N-Benzyl Residues as the P1′ Substituents in Phosphorus-Containing Extended Transition State Analog Inhibitors of Metalloaminopeptidases
2020
Peptidyl enzyme inhibitors containing an internal aminomethylphosphinic bond system (P(O)(OH)-CH2-NH) can be termed extended transition state analogs by similarity to the corresponding phosphonamidates (P(O)(OH)-NH). Phosphonamidate pseudopeptides are broadly recognized as competitive mechanism-based inhibitors of metalloenzymes, mainly hydrolases. Their practical use is, however, limited by hydrolytic instability, which is particularly restricting for dipeptide analogs. Extension of phosphonamidates by addition of the methylene group produces a P-C-N system fully resistant in water conditions. In the current work, we present a versatile synthetic approach to such modified dipeptides, based…
Study of the role of “gatekeeper” mutations V654A and T670I of c-kit kinase in the interaction with inhibitors by means mixed molecular dynamics/dock…
2011
The over-expression of c-kit proto-oncogene has been reported in hematopoietic cells, small cell lung cancer, and gastrointestinal stromal tumors. The clinical importance of c-kit expression in tumors focused the research towards inhibitors of this tyrosine kinase. Imatinib (Gleevec®) was the first compound used in therapy, but mutations on c-kit led to reduced effectiveness or ineffectiveness of this treatment. Other compounds are likely to be effective against mutants, such as Sunitinib (Sutent®), but the need for new and most effective inhibitors against mutants is still critical. We report mixed Molecular Dynamics/Docking study with the aim to unveil the molecular mechanism involved in …
The Use of Game World Tasks Concepts in Higher Education
2016
The link between tasks presented in games and tasks used in higher education might have more in common than we think. Analysing how tasks work in games and applying those structures to higher education teaching can enable teachers to develop more creative, situated and exciting tasks for their students. In addition, it can improve communication and feedback. Analysis shows that tasks are an area where elements of gamification work. This article looks into the possibility of reproducing the flexibility and key components of game tasks in actual tasks in higher education. We look at the challenges and limitations and ways to solve them. Therefore, we analyse the concept of quest-logs in games…
Overload of Medical Documentation: A Disincentive for Healthcare Professionals
2020
This review addresses the theories concerning the development and functioning of medical bureaucracy creating an excess of the patient records. An ever-growing number of medical files comply with the typical development of the bureaucratic management of an entrepreneurial organization, an essential feature of which is the life cycle of documentation. When the life cycle ends, an update is created with a multiplication of forms and items to be filled out, resembling that of what happens with the outdated computer program. Yet medical records should have a logical and well-functioning structure using the language of computer science in the form of a cascade or evolutionary model. Further, we …
A framework for PACS development in cardiology
2003
The authors develop a framework for the integration of cardiology into hospitalwide picture archiving and communication systems (PACSs) by the definition of user requirements in cardiology image information systems. These user requirements have to be based on the consensus of users and industry. A topdown layered scheme is proposed for the development of documents based on user requirements. The structure of committees within the European Society of Cardiology that are working in this field is discussed. >