Las personas en exclusión social que padecen múltiples problemas de salud suelen experimentar un agravamiento y cronificación progresivas de sus dificultades a escala individual (salud mental), ...familiar (conflictos, rupturas) y social (exclusión, aislamiento), lo cual hace necesario establecer herramientas de acompañamiento específicas que les permitan mantenerse en los procesos de inserción y avanzar en su calidad de vida e integración social. Este artículo presenta el modelo Integra/Erantsi, destinado a facilitar el acompañamiento psicosocial en procesos de inclusión a personas con múltiples problemas sociales y de salud asociados a adicciones o a enfermedades psiquiátricas. El modelo se ha plasmado en una guía de acompañamiento y se ha implantado en los últimos años en la Asociación T4 de Lucha contra el Sida, habiéndose observado mejoras significativas en las dimensiones de apoyo social, relaciones sociales, ajuste social y ansiedad entre las personas usuarias de la entidad.
Telomeres and telomerase are key players in tumorogenesis. Among the various strategies proposed for telomerase inhibition or telomere uncapping, the stabilization of telomeric G-quadruplex (G4) ...structures is a very promising one. Additionally, G4 stabilizing ligands also act over tumors mediated by the alternative elongation of telomeres. Accordingly, the discovery of novel compounds able to act on telomeres and/or inhibit the telomerase enzyme by stabilizing DNA telomeric G4 structures as well as the development of approaches efficiently prioritizing such compounds constitute active areas of research in computational medicinal chemistry and anticancer drug discovery. In this direction, we applied a virtual screening strategy based on the rigorous application of QSAR best practices and its harmonized integration with structure-based methods. More than 600,000 compounds from commercial databases were screened, the first 99 compounds were prioritized, and 21 commercially available and structurally diverse candidates were purchased and submitted to experimental assays. Such strategy proved to be highly efficient in the prioritization of G4 stabilizer hits, with a hit rate of 23.5%. The best G4 stabilizer hit found exhibited a shift in melting temperature from FRET assay of +7.3 °C at 5 μM, while three other candidates also exhibited a promising stabilizing profile. The two most promising candidates also exhibited a good telomerase inhibitory ability and a mild inhibition of HeLa cells growth. None of these candidates showed antiproliferative effects in normal fibroblasts. Finally, the proposed virtual screening strategy proved to be a practical and reliable tool for the discovery of novel G4 ligands which can be used as starting points of further optimization campaigns.
Guanine-rich sequences found at telomeres and oncogenes have the capacity to form G-quadruplex (G4) structures. It has been found a relationship between the ability to stabilizing G4 structures and ...anticancer activity. Guanine quadruplexes stabilization and its implication in cancer phenomena is a therapeutic target relatively recent. Computer-aided drug design has been a very useful tool for the search of new candidates. In last years, methodologies have improved with the development of the computational sciences. The hardware is also enhanced, new techniques are explored. NMR and X-ray information about different targets are discovered continually. The continuous augmentation of new powerful and comprehensive software's with this purpose is other significant factor that contributes to the discovering of new compounds. Nevertheless computer-aided drug design has not been vastly employed in the design of new compound with G4 stabilization activity. All things considered, this review will be focused on the influence of computational techniques on speeding up the discovery of new G4 ligands.
ADSORCIÓN DE IONES Cd (II) EN TALQUITA Prieto García, Julio Omar; Quintana Puchol, Rafae; Quero Jiménez, Pedro Cesar ...
Centro azúcar,
12/2021, Letnik:
48, Številka:
4
Journal Article
Odprti dostop
RESUMEN Introducción: La talquita consta de paquetes alternados de tres capas con enlaces débiles de Van der Waals entre ellos. La capa octaédrica se encuentra entre dos capas tetraédricas. Es ...utilizada como adsorbente de metales pesados en solución acuosa. Objetivo: Determinar el modelo cinético, la difusividad efectiva y las isotermas correspondientes a la adsorción en el sistema heterogéneo de masa solución acuosa de iones Cd (II) y talquita a las temperaturas de 298 y 333 K. Materiales y Métodos: Se realiza una caracterización física y química del adsorbente. El estudio cinético, difusivo y de equilibrio de adsorción de iones se lleva a cabo a 298 y 333 K. Los procesos de adsorción se llevan a cabo con agitación a 150 rpm en un agitador mecánico. Se instrumentan los modelos de seudoprimer orden, seudosegundo orden, Elovich, difusión en la película de líquido, difusión intrapartícula, modelo de Bangham y difusión efectiva. Para los estudios de equilibrio isotérmicos se implementan las isotermas de Langmuir, Freundlich, Dubinin- Radushkevich, BET, Redlich, Toth y Flory-Huggins. Las concentraciones se determinan por Espectroscopía de Absorción Atómica. Resultados y Discusión: El modelo cinético de seudoprimer orden es el que mejor ajusta a la cinética de la adsorción a las dos temperaturas estudiadas. Los modelos isotérmicos de BET a 298 K y Flory - Huggins a 333 K son los que mejor ajustan a la adsorción de los iones Cd (II) en solución acuosa. Conclusiones: La talquita presenta moderadas capacidades de adsorción de los iones Cd (II) en solución acuosa.
Guanine-rich sequences found in telomeres and oncogene promoters have the ability to form G-quadruplex structures. In this paper we describe the use of a virtual screening assay to search a database ...of FDA-approved compounds for compounds with the potential to bind G-quadruplex DNA. More than 750 telomerase inhibitors were identified in a literature search as acting through G-quadruplex stabilization, and from evaluation of these compounds, theoretical models capable of discriminating new compounds that bind G-quadruplex DNA were developed. Six compounds predicted to bind to the G-quadruplex structure were tested for their ability to bind to the human telomeric DNA sequence. Prochloroperazine, promazine, and chlorpromazine stabilized the G-quadruplex structure as determined by fluorescence resonance energy transfer techniques. These compounds also bound to promoter sequences of oncogenes such as c-myc and K-ras. Amitriptyline, imipramine, and loxapine were less stabilizing but did bind to the G-quadruplex. The ability of prochloroperazine, promazine, and chlorpromazine to recognize G-quadruplex structures was confirmed using a fluorescent intercalator displacement assay, in which displacement of thiazole orange from G-quadruplex structures was demonstrated. Interestingly, these compounds exhibited selectivity for the G-quadruplex structure as all had poor affinity for the duplex sequence.
En la investigación se aborda el estudio cinético y termodinámico de la adsorción de iones uranilo en solución acuosa con el uso de ceniza de bagazo de caña de azúcar. Desde el punto de vista ...cinético es una adsorción física que refrenda al modelo de seudoprimer orden donde el mecanismo difusivo a través de la película de líquido es fundamental. Los modelos de Freundlich y Dubinin responden desde el punto de vista termodinámico a la adsorción de los iones en solución acuosa
Esta investigación está relacionada con la cinética de adsorción de los iones manilo en dióxido de silicio amorfo. Los datos experimentales fueron analizados a través de varios modelos cinéticos: ...seudoprimer orden, seudosegundo orden, Elovich, difusión intrapartícula, modelo de Bangham y difusión en la película de líquido. El modelo de Seudosegundo orden es el que mejor describe, desde el punto de vista cinético, la adsorción de iones uranilo en el sólido.
INFECCIÓN POR VIH: TÉCNICAS DE DETECCIÓN Daimel Castillo González; Olga Lidia González González; María Boffill Cárdenas
Medicentro (Villa Clara),
09/2011
Journal Article
Recenzirano
Odprti dostop
El diagnóstico serológico del virus de la inmunodeficiencia humana (VIH) trasciende en importancia a otros diagnósticos de laboratorio, por la gravedad de la enfermedad que este virus produce, la ...existencia hoy en día de tratamientos mucho más eficaces que los iniciales y el conocimiento que tienen los médicos y sanitarios sobre esta infección.
Les séquences d’ADN et d'ARN riches en Guanines peuvent adopter des conformations inhabituelles connues sous le nom de G-quadruplexes (G4). Les topologies et les formes de ces structures fascinantes ...sont très diverses. Les G4 sont stabilisés par la présence de cations monovalents et des liaisons Hydrogène de type Hoogsteen. De petites molécules contribuent également à la formation de formes stables, principalement par des interactions d'empilement π - π. Bien que les G4 soient connus depuis des décennies, l'intérêt de la communauté scientifique a été stimulé par la découverte de leur effet potentiellement inhibiteur sur la télomérase, une transcriptase inverse impliquée dans la transformation maligne de la plupart des cellules cancéreuses. En ce qui concerne la télomérase, le cancer et G4, plusieurs groupes ont été impliqués dans la découverte de nouveaux stabilisateurs G4 qui peuvent indirectement inhiber l'enzyme. Des centaines de ligands ont été identifiés par ce biais au cours de la dernière décennie et c'est encore un domaine très actif. Prenant en compte les avantages et la facilité qu'offre l'identification de nouvelles structures à l'aide de techniques de calcul grâce à des modèles mathématiques simples et reproductibles, nous avons entrepris un criblage à haut débit et à faible coût de calcul afin d’identifier de nouveaux ligands G4. Avec l'utilisation de la modélisation QSAR nous pouvons prédire l’IC50 d'un ensemble de composés congénères. Nous avons également été en mesure de relier les descripteurs moléculaires qui apparaissent dans nos modèles avec des caractéristiques structurales que les études de la littérature scientifique et SAR ont rapportés dans les études précédentes, pour un ensemble de ligands congénères. En outre, nous avons construit des modèles différents utilisant des ensembles non congénères de composés en appliquant une stratégie de consensus et pu identifier six ligands approuvés par la FDA qui stabilisent les structures G4. Par la suite, en appliquant des techniques non linéaires et un processus pour le traitement de la base de données que nous avons contruite à partir de publications antérieures, nous avons effectué un criblage virtuel de plus de 500 000 ligands d'une base de données commerciale de composés. Nous avons pu identifier de nouveaux ligands avec une puissance plus forte que les précédentes, qui peuvent également stabiliser d’autres structures G4 impliqués dans les processus liés au cancer. Ces observations ouvrent un spectre large de possibilités à explorer. Malgré les limites des techniques de modélisation QSAR explorées tout au long de ce travail, nous considérons qu'elles peuvent être combinées et utilisées avec soin pour répondre à la recherche de nouveaux stabilisateurs G4.
DNA and RNA G-rich sequences can adopt unusual arrangements that are known as G-quadruplexes (G4). The topologies and forms of these fascinating structures are very diverse. G4 are stabilized by the presence of monovalent cations and Hoogsteen Hydrogen bonds. Small molecules also contribute to the formation of stable forms mainly via π-π stacking interactions. Although G4s are known for decades, interest in this field started with their potential effect on inhibition of telomerase enzyme, a Reverse Transcriptase involved in the malignant transformation of most cancer cells. With regards to telomerase, cancer and G4, several groups have been involved in the discovery of new G4 stabilizers that would indirectly inhibit the enzyme. Most of the G4 ligands were identified following this paradigm. Hundreds of ligands have been identified during the past decade and this is still a very active field in science. Taking into account the advantages and easiness that offers the identification of new structures using computational techniques we built single and reproducible mathematical models with high screening capacity and low computational cost in order to use them on the identification of G4 ligands. With the use of QSAR modelling we can predict the telIC50 of a congeneric set of compounds. We have also been able to relate the molecular descriptors that appear in ours models with some structural features that scientific literature and SAR studies have reported in previous studies as appropriated for describing the above mentioned activity, also for congeneric set of ligands. Moreover, we built different models using non congeneric sets of compounds applying a consensus strategy and could identify six FDA approved ligands that stabilize G4 structures. Subsequently, by applying nonlinear techniques and a process for the cure of the database proposed for us in previous publications, we have performed a virtual screening of more than 500 000 ligands from a commercial database of compounds, followed of structure-based model in order to reduce the number of candidates. We were able to identify new ligands with stronger potency than the previous ones, which can also stabilize other G4 structures involved in processes related to cancer. These observations open a wide-ranging spectrum of possibilities to be explored. Despite the limitations of the QSAR modelling techniques explored along this work, we consider they can be combined and used carefully to address the search for new G4 stabilizers.
Telomerase is a reverse transcriptase enzyme that activates in more than 85% of cancer cells and it associated with the acquisition of a malignant phenotype. Some experimental strategies have been ...suggested in order to avoid the enzyme effect on unstopped telomere elongation. One of them, the stabilization of the G‐quartet structure, has been widely studied. Nevertheless, no QSAR studies to predict this activity have been developed. In the present study, several regression models were developed to identify, through 3‐D molecular descriptors, those acridinic derivatives with better inhibitory activity on the telomerase enzyme (log telEC50). Linear regression models were developed from a dataset of 85 acridinic derivatives and the best results were achieved using GETAWAY and WHIM molecular descriptors. The final model explained 80% of the variance and the predictive ability was assessed by a leave‐one‐out cross‐validation (Q$\rm{ _{{\rm{LOO}}}^2 }$=74.3), a prediction set (21 compounds of the 85; R$\rm{ _{{\rm{pred}}}^2 }$=71.50 and SDEPpred=0.366), and the prediction of inhibitory activity on telomerase enzyme for external set of ten novel acridines. The results of this study suggest that the established model has a strong predictive ability and can be prospectively used in the molecular design and action mechanism analysis of this kind of compounds with anticancer activity.
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