Stability of Dirac cone in artificial graphene

Trabajo presentado al 18th ETSF Workshop celebrado en Luxemburgo del 1 al 4 de Octubre de 2013.ETSF - European Theoretical Spectroscopy Facility I3 (211956).Peer Reviewe

Studio dei danni indotti da radiazioni non ionizzanti, UV e luminosa ad alta frequenza, a livello delle cellule staminali limbari

Il danno oculare da radiazioni luminose riguarda normalmente la cornea, ma può coinvolgere la retina. La cornea è la porzione anteriore dell'occhio e riceve il suo nutrimento dalle anse vascolari del limbus o giunzione sclero-corneale da cui provengo anche le cellule in grado di sostituire le cellule della cornea danneggiate. L’oftalmia da irradiazione luminosa è una lesione causata dalle radiazioni solari, conosciuto anche come "danno da luce blu", e/o da UV; la patologia è in grado di procurare dolore e arrossamento degli occhi e danni cicatriziali talvolta irreversibili. Per tali danni è stato suggerita una eziologia apoptotica mitocondriale oltre a normali eventi necrotici. Un elevato contenuto di ROS accelera la comparsa e la gravità dei danni da fotocheratite. Risulta importante proteggere e/o trattare farmacologicamente chi fosse stato esposto accidentalmente o continuativamente a rilevante irraggiamento, quali per esempio piloti di aereo, oppure particolari popolazioni. Per limitare tali danni utilizzare lenti filtranti non sembra essere in grado di risolvere il problema, soprattutto in soggetti già esposti. Diviene necessario studiare presidi farmacologici atti ad eliminare o ridurre eventuali rischi di danno irreversibile. Per ottimizzare tale studio si propone la valutazione delle risposte su sistemi in vitro che utilizzino colture cellulari quali: epiteliali; cheratociti e cellule staminali da espianti di limbus Su tali cellule si può indurre citoprotezione al fine di ridurne il danno da radiazioni, somministrando farmaci in grado di interferire con i meccanismi degenerativi, in particolare per prevenire danni al livello del DNA indotti da UVa/b

Development of novel phenoxyalkylpiperidines as high-affinity Sigma-1 (σ1) receptor ligands with potent anti-amnesic effect

International audienceThe sigma-1 (σ1) receptor plays a significant role in many normal physiological functions and pathological disease states, and as such represents an attractive therapeutic target for both agonists and antagonists. Here, we describe a novel series of phenoxyalkylpiperidines based on the lead compound 1-[ω-(4-chlorophenoxy)ethyl]-4-methylpiperidine (1a) in which the degree of methylation at the carbon atoms alpha to the piperidine nitrogen was systematically varied. The affinity at σ1 and σ2 receptors and at Δ8-Δ7 sterol isomerase (SI) ranged from subnanomolar to micromolar Ki values. While the highest-affinity was displayed at the σ1, the increase of the degree of methylation in the piperidine ring progressively decreased the affinity. The subnanomolar affinity 1a and 1-[ω-(4-methoxyphenoxy)ethyl]-4-methylpiperidine (1b) displayed potent anti-amnesic effects associated with σ1 receptor agonism, in two memory tests. Automated receptor-small-molecule ligand docking provided a molecular structure-based rationale for the agonistic effects of 1a and 1b. Overall, the class of the phenoxyalkylpiperidines holds potential for the development of high affinity σ1 receptor agonists, and compound 1a, that appears as the best in class (exceeding by far the activity of the reference compound PRE-084) deserves further investigation

DEVELOPMENT OF PHENOXYALKYLPIPERIDINES AS HIGH-AFFINITY SIGMA-1 (s1) RECEPTOR LIGANDS WITH POTENT ANTI-AMNESIC ACTIVITY

The sigma-1 (σ1) receptor plays a significant role in many physiological functions and pathological disease states, and, as such, it represents an attractive therapeutic target for both agonists and antagonists. Here, we describe a novel series of phenoxyalkylpiperidines (Figure 1) that were prepared and tested at σ1, σ2, and sterol Δ8- Δ7 isomerase (SI) sites by in vitro radioligand binding assays. These new compounds are derivatives of the σ ligand 1-[3-(4-chlorophenoxy)propyl]-4-methylpiperidine (L1), which has been claimed as a therapeutic agent for CNS disorders and neuropathies. In order to explore the structure-affinity relationships (SAFIRs) of this class of compounds, we modified the aryloxyl and piperidine moieties and the linker that connects them. In particular, we evaluated the influence of the stereochemistry on σ receptors affinity and selectivity through the introduction of methyl groups either on the chain or on the piperidine ring. The affinity at σ1 and σ2 receptors and at Δ8-Δ7 sterol isomerase (SI) ranged from subnanomolar to micromolar Ki values. While the highest affinity was displayed at the σ1 receptor (Ki = 0.34 nM), the chirality introduced by a methyl substitution in the linker resulted only in slight differences. The higher was the degree of methylation on the piperidine ring the lower was the ligand affinity, in agreement with other classes of σ1 receptor ligands. Nevertheless, the shorter oxyethylenic chain was beneficial for the σ1 selectivity. Importantly, these shorter-chain compounds displayed potent antiamnesic effects associated with σ1 receptor agonism, in two different memory tests. Overall, phenoxyalkylpiperidines hold potential for the development of high affinity σ1 receptor agonists

Le applicazioni della Chimica Farmaceutica di Camille G. Wermuth

Medicinal Chemistr