Search results for " DOC"
showing 10 items of 1281 documents
Ensemble-based ADME-Tox profiling and virtual screening for the discovery of new inhibitors of the Leishmania mexicana cysteine protease CPB2.8ΔCTE
2018
Abstract: In an effort to identify novel molecular warheads able to inhibit Leishmania mexicana cysteine protease CPB2.8CTE, fused benzo[b]thiophenes and ,'-triketones emerged as covalent inhibitors binding the active site cysteine residue. Enzymatic screening showed a moderate-to-excellent activity (12%-90% inhibition of the target enzyme at 20m). The most promising compounds were selected for further profiling including in vitro cell-based assays and docking studies. Computational data suggest that benzo[b]thiophenes act immediately as non-covalent inhibitors and then as irreversible covalent inhibitors, whereas a reversible covalent mechanism emerged for the 1,3,3'-triketones with a Y-to…
Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D
2017
A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.
Comparative analysis of virtual screening approaches in the search for novel EphA2 receptor antagonists
2015
The EphA2 receptor and its ephrin-A1 ligand form a key cell communication system, which has been found overexpressed in many cancer types and involved in tumor growth. Recent medicinal chemistry efforts have identified bile acid derivatives as low micromolar binders of the EphA2 receptor. However, these compounds suffer from poor physicochemical properties, hampering their use in vivo. The identification of compounds able to disrupt the EphA2-ephrin-A1 complex lacking the bile acid scaffold may lead to new pharmacological tools suitable for in vivo studies. To identify the most promising virtual screening (VS) protocol aimed at finding novel EphA2 antagonists, we investigated the ability of…
Russian concept of the Eurasian Aerospace Defense System. Analysis of the problem
2018
The author of the article describes the most important theses of A. Podberezkin plan against the geopolitical Russia background which form a paradigm of a common security in Russian terms on a strategic area of Eurasia. It is of a particular significance in view of the growing threats to modern world. Especially of hazardous nature is current problem of North Korea in connection with nuclear testing carried out by unpredictable regime of Kim Jong-un which creates the risk that sudden conflict can drag the whole Peninsula into a war. This, in turn, would lead to the US intervention there. Effects of the possible conflict involving superpower are hard to predict. Another current problem is Mo…
Progettazione e sintesi di nuovi derivati 4-chinazolinonici potenziali inibitori della diidrofolato reduttasi
2018
I chinazolinoni sono composti eterociclici azotati che, insieme alle chinazoline, rappresentano degli importanti farmacofori in possesso di un ampio spettro di proprietà biologiche tra cui quella antitumorale. Recentemente sono stati riportati in letteratura dei derivati 4-chinazolinonici in grado di inibire in vitro l’enzima diidrofolato reduttasi (DHFR) con IC50 comprese tra 0.4 e 1.0 µM [1]. Allo scopo di progettare la sintesi di nuovi potenziali inibitori della DHFR, è stato condotto uno studio di modellistica molecolare considerando tale enzima come biotarget. Tale studio ha portato alla selezione di 42 nuovi derivati 4-chinazolinonici (Figura 1). Attualmente, sono stati sintetizzati 2…
In Vitro and In Silico Studies of Two 1,4-Naphthoquinones and Their Topical Formulation in Bigels.
2021
Background: 1,4-Naphthoquinones (1,4-NQs) are secondary plant metabolites with numerous biological activities. 1,4-NQs display low water solubility and poor bioavailability. Bigels are a new technology with great potential, which are designated as drug delivery systems. Biphasic bigels consisting of solid and liquid components represent suitable formulations improving diffusion and bioavailability of NQs into the skin. Objective: We evaluated the in silico and in vitro activity of 5,8-dihydroxy-1,4-naphthoquinone (M1) and 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (M2) on elastase and assessed their cytotoxicity towards COLO38 melanoma cells. The 1,4-NQs were loaded into bigels for topi…
HL7v3 CDA Rel.2 Patient Summary and Chronic Care Model: Localization experience and GP/HS Integration Project
2010
The localization experience for the Patient Summary, based on the Health Level Seven Version 3 (HL7v3) Clinical Document Architecture, Release 2 (CDA Rel.2), is presented. An overview of the Chronic Care Model (CCM) is introduced with particular attention to the clinical information systems, in order to organize patient and population clinical data by sharing information among healthcare providers in management of chronic diseases. We propose, as case study, a project for the integration of various services for General Practitioners (GP) and Hospital Specialists (HS), accessing the Electronic Health Record (EHR), implementing the Patient Summary and managing the exchange of Chronic Care med…
“Team Based Learning” in Political Science studies
2019
En los estudios de Ciencia Política ha predominado tradicionalmente la metodología basada en la clase magistral y el trabajo individual. Sin embargo, la implantación del sistema de Bolonia implica un trabajo más autónomo de los estudiantes y el desarrollo de nuevas habilidades como el trabajo en grupo. Desde esta perspectiva, se ha aplicado una nueva metodología denominada Aprendizaje Basado en Grupos (TBL de sus siglas en inglés) a un grupo de 100 alumnos de Ciencia Política y se la ha comparado con otros tres métodos también utilizados por los mismos estudiantes en otras asignaturas del grado (práctica semanal, trabajo semestral y Aprendizaje Basado en Problemas). El objetivo del trabajo …
NO-DO, el tiempo y la memoria [Prólogo a la octava edición]
2006
EL Noticiario Cinematográfico Español, popularmente conocido como NO-DO, vio las pantallas cinematográficas por vez primera en enero de 1943. Creado como instrumento audiovisual del nuevo Estado, gozó durante décadas del privilegio de su exclusividad y su proyección fue obligatoria en todos los cines de España. A pesar de los numerosos cambios que experimentó la sociedad española, el Noticiario permanece hasta bien entrada la democracia, en 1981. Pero NO-DO no fue sólo un instrumento de propaganda política. Su condición de noticiario cinematográfico hace de él un dispositivo informativo, bien que sesgado, de entretenimiento y de variedades que acompañaba puntualmente los programas de las sa…
Los límites de la subjetividad en la vanguardia documental japonesa. El caso de Hōryūji (Susumu Hani, 1958)
2018
Este artículo pretende contribuir al redescubrimiento de la vanguardia documental japonesa a través de la figura de Susumu Hani (1928- ), quien tuvo un papel clave tanto por su aportación teórica como práctica. Hōryūji (1958) representa una las propuestas más atrevidas para desarrollar la subjetividad entre los cineastas de la nueva a izquierda. Este singular documental debe entenderse a la luz de los escritos donde Hani afirma que es posible acceder a subjetividades ajenas al director a través de ciertos tipos de "protagonistas que no actúan".