Search results for " DOC"
showing 10 items of 1281 documents
Activity of the dietary flavonoid, apigenin, against multidrug-resistant tumor cells as determined by pharmacogenomics and molecular docking
2015
Apigenin is a common dietary flavonoid with considerable cytotoxic activity in vitro and in vivo. Despite many mechanistic studies, less is known about resistance factors hampering apigenin's activity. We investigated the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5. Multidrug-resistant cells overexpressing these ABC transporters were not cross-resistant toward apigenin. Moreover, apigenin inhibited not only P-glycoprotein but also BCRP by increasing cellular uptake of doxorubicin and synergistic inhibition of cell viability in combination with doxorubicin or docetaxel in multidrug-resistant cells. To perform in silico molecular docki…
Algunas reflexiones acerca de la stjue de 9 de julio de 2020 sobre los pactos novatorios en materia de cláusulas suelo
2021
The Sentence of the Court of Justice of the European Union of July 9, 2020 comes to answer the five questions that, in its preliminary question, the Court of First Instance and Instruction No. 3 of Teruel asks about the validity of the new agreements in the context of the floor clauses, establishing jurisprudential doctrine on this matter about which our Supreme Court had previously ruled in its Judgments of October 16, 2017, in the sense of considering the agreed floor clause null as a consequence of the novation agreement and, subsequently, those of April 11, 2018 and September 13, 2018 in the opposite direction, declaring that the novation agreement was valid. It is a long-awaited and in…
Carrera profesional del maestro de obras del rey en el Reino de Valencia en época de los en la época de los Austrias: la sucesión al cargo que ocupó …
2009
El maestro de obras reales en el Reino de Valencia se ocupó de la supervisión de los trabajos en los bienes inmuebles del patrimonio regio, que incluía arquitectura e ingeniería civil, militar e hidráulica. Presentamos el informe enviado por el virrey en 1622 sobre los tres candidatos al cargo: Antonio Picó, Jerónimo Negret y Francisco Arboreda (o Arboleda). Resulta especialmente interesante la información sobre este último, que lo ocupó hasta 1636, pues en la exposición de méritos, por un lado, ofrece información sobre las obras realizadas por sus ancestros, Joan Arboreda, que identificamos con el Joan Navarro que ocupó el mismo cargo en las décadas centrales del siglo XVI, y Jerónimo Arbo…
Valutare i cartoni animati. Un'attività di formazione dei futuri insegnanti della Scuola dell'Infanzia
2008
Il contributo presenta la progettazione e realizzazione di un intervento formativo la cui finalità è stat quella di far riflettere gli studenti universitari, di Scienze della Formazione Primaria di Palermo, sulla fondamentale importanza di una valutazione adeguata e valida, quale condizione indispensabile per un efficace lavoro educativo. Inl particolare si è focalizzata l'attenzione sulla capacità di formulare giudizi adeguati, utilizzando indicatori per la valutazione dei cartoni animati trasmessi in tv e destinati a bambini della prima infanzia.
Los castillos valencianos en el siglo XIII. Del "hisn" musulmán al "castrum" cristiano
2004
Las fuentes escritas en su doble vertiente cronística y documental y el examen de os restos materiales, que sin necesidad de excavación previa aún se pueden contemplar, son nuestras bases de apoyo de este análisis. Ellas son las que, a su vez, delimitan la cronología y permiten que se centre de forma especial en época cristiana. El primer tipo de construcción castral estaba formada por tres partes: una primera la integraban una serie de construcciones ubicadas en su parte superior, que sólo en algunos casos podernos denominara alcazaba. A continuación hay que citar el albacar y, por último, una medina o ciudad de amplia superficie en su parte baja. El segundo grupo de castillos estaba integ…
Synthesis, In Vitro and In Silico Analysis of New Oleanolic Acid and Lupeol Derivatives against Leukemia Cell Lines: Involvement of the NF-κB Pathway
2022
Oleanolic acid (OA) and Lupeol (LU) belong to the class of natural triterpenes and are endowed with a wide range of biological activities, including cytotoxicity toward several cancer cell lines. In this context, we investigated a set of compounds obtained from the two natural precursors for the cytotoxicity against leukemia HL60 cells and the multidrug-resistant (MDR) variant HL60R. Six new semi-synthetic triterpenes have been synthetized, fully characterized, and were investigated together with other triterpenes compounds for their pharmacological mechanism of action. The interaction of the more cytotoxic compounds with the nuclear factor kappa B (NF-κB) pathway has been also evalua…
Kinetic and thermodynamic insights into interaction of erlotinib with epidermal growth factor receptor: Surface plasmon resonance and molecular docki…
2020
Abstract Epidermal growth factor receptor (EGFR) plays an important role in cell proliferation at non-small cell lung cancer (NSCLC). Therefore, targeted therapy of cancer via this kind of receptor is highly interested. Small molecule drugs such as erlotinib and gefitinib inhibit EGFR tyrosine kinase and thus suppress cell proliferation. At this paper, erlotinib interaction with EGFR on the cell surface was studied via surface plasmon resonance (SPR) and molecular docking methods. Kinetic parameters indicated that erlotinib affinity toward EGFR was increased through increment of temperature. The thermodynamic analysis showed that van der Waals and hydrogen binding forces play a major role i…
A novel moniliformin derivative as pan-inhibitor of histone deacetylases triggering apoptosis of leukemia cells
2021
New and potent agents that evade multidrug resistance (MDR) and inhibit epigenetic modifications are of great interest in cancer drug development. Here, we describe that a moniliformin derivative (IUPAC name: 3-(naphthalen-2-ylsulfanyl)-4-{[(2Z)-1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene]methyl}cyclobut-3-ene-1,2-dione; code: MCC1381) bypasses P-gp-mediated MDR. Using transcriptomics, we identified a large number of genes significantly regulated in response to MCC1381, which affected the cell cycle and disturbed cellular death and survival. The potential targets of MCC1381 might be histone deacetylases (HDACs) as predicted by SwissTargetPrediction. In silico studies confirmed that MCC13…
Polyketides from the marine-derived fungus Aspergillus falconensis: In silico and in vitro cytotoxicity studies.
2020
Abstract Fermentation of the marine-derived fungus Aspergillus falconensis, isolated from sediment collected from the Red Sea, Egypt on solid rice medium containing 3.5% NaCl yielded a new dibenzoxepin derivative (1) and a new natural isocoumarin (2) along with six known compounds (3–8). Changes in the metabolic profile of the fungus were induced by replacing NaCl with 3.5% (NH4)2SO4 that resulted in the accumulation of three further known compounds (9–11), which were not detected when the fungus was cultivated in the presence of NaCl. The structures of the new compounds were elucidated by HRESIMS and 1D/2D NMR as well as by comparison with the literature. Molecular docking was conducted fo…
Computational Evaluation and In Vitro Validation of New Epidermal Growth Factor Receptor Inhibitors
2020
Background:The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein that acts as a receptor of extracellular protein ligands of the epidermal growth factor (EGF/ErbB) family. It has been shown that EGFR is overexpressed by many tumours and correlates with poor prognosis. Therefore, EGFR can be considered as a very interesting therapeutic target for the treatment of a large variety of cancers such as lung, ovarian, endometrial, gastric, bladder and breast cancers, cervical adenocarcinoma, malignant melanoma and glioblastoma.Methods:We have followed a structure-based virtual screening (SBVS) procedure with a library composed of several commercial collections of chemicals (615,46…