38 research outputs found
Design and synthesis of phosphonoacetic acid (PPA) ester and amide bioisosters of ribofuranosylnucleoside diphosphates as potential ribonucleotide reductase inhibitors and evaluation of their enzyme inhibitory, cytostatic and antiviral activity.
Continuing our investigations on inhibitors of ribonucleotide reductase (RNR), the crucial enzyme that catalyses the reduction of ribonu-cleotides to deoxyribonucleotides, we have now prepared and evaluated 5′-phosphonoacetic acid, amide and ester analogues of adenosine, uridine and cytidine with the aim to verify both substrate specificity and contribution to biological activity of diphosphate mimic moieties. A molecular modelling study has been conducted on the RNR R1 subunit, in order to verify the possible interaction of the proposed bioisosteric moieties. The study compounds were finally tested on the recombinant murine RNR showing a degree of inhibition that ranged from 350 μM for the UDP analogue 5′-deoxy-5′- N-(phosphon-acetyl)uridine sodium salt (amide) to 600 μM for the CDP analogue 5′- O-[(diethyl-phosphon)acetyl]cytidine (ester). None of the tested compounds displayed noteworthy cytostatic activity at 100–500 μM concentrations, whereas ADP analogue 5′- N-[(diethyl-phosphon) acetyl]adenosine (amide) and 5′-deoxy-5′- N-(phos-phon-acetyl)adenosine sodium salt (amide) showed a moderate inhibitory activity (EC50: 48 μM) against HSV-2 and a modest inhibitory activity (EC50: 110 μM) against HIV-1, respectively
Hindered nucleoside analogs as antiflaviviridae agents
Abstract
Flaviviridae are an important family of viruses, responsible for widely spread diseases such as dengue and West Nile fever and hepatitis C. Despite the severity of the related diseases, no effective antiviral treatments for infection are available. Following our discovery of adenosine-hindered analogs as potent antiflaviviridae agents, we have continued our investigation on guanosine and inosine derivatives, which were evaluated for activity against BVDV, YFV, DENV, and WNV viruses in cell-based assays. The present study allowed us to identify some newer features that led to improve the antiviral potency (down to the µM range) and to selectively inhibit BVDV and YFV viruses. The molecular modeling results were consistent with the hypothesis that test analogs act as RNA-dependent RNA polymerase (RdRp) inhibitors by interacting with a surface allosteric binding pocket
Cornici di tortura Lo scandalo di Abu Ghraib come rituale mediatizzato tra fotogiornalismo e arte contemporanea
This paper deals with the scandal of Abu Ghraib. The diffusion of the torture photographs is analyzed as a peculiar form of mediatized ritual, which has cristallized them in the public memory and performatively activated a number of practices of creative re-contextualization and symbolic re-articulation. In particular, the paper problematizes a wide range of forms of artistic representations of the torture photographs, according to three main analytical dimensions: inter-iconic translation, authorial intentions, degree of institutionalization
Fotografia documentaria, corpi politici e maschere sociali
Il paper analizza e contestualizza il progetto editoriale del libro prevalentemente fotografico "Il Corpo del Capitano", evidenziandone contenuti e valenza estetica, politica e culturale, anche in relazione a più ampie dinamiche interne al campo giornalistico,
fotografico e artistico. Il paper ne interpreta il processo di produzione e le scelte stilistiche e comunicative come esempio evidente di mutamenti di linguaggio e posizionamento in atto nel campo professionale della fotografia giornalisticodocumentaria
e dell’informazione visiva nell’era digitale, ricostruendone le istanze di costruzione di uno statuto autoriale potenzialmente soggetto a consacrazione artistica, e soffermandosi al contempo sul ruolo simbolico e metaforico della «maschera» fotografica di Salvini realizzata come evocativa copertina del volume, a partire dalla copertina del settimanale «Time» con la stessa immagine, pubblicata a introduzione di un editoriale critico nei confronti del crescente potere salviniano ma ripreso e decontestualizzato dalla macchina comunicativa del leader a fini propagandistici e celebrativi
VITE MOBILI
In un passato ancora prossimo l’identità personale veniva costruita sulle radici, sull’appartenenza a un luogo e sui legami con esso. Oggi tutto questo è ormai sostituito dalla capacità di servirsi, approfittare e anche godere di una mobilità , fisica e virtuale, praticamente illimitata: dal pendolarismo tra mutevoli sedi di vita e di lavoro, al flusso ininterrotto di informazioni globali in rete; dal turismo al consumo crescente di merci de-localizzate; dalla possibilità di comunicare con chiunque praticamente da ogni luogo allo sviluppo di relazioni intime a distanza. Esperienze inedite, che portano con sé benefici straordinari ma anche costi non sempre immediatamente visibili
News Photography and the Digital (R)evolution: Continuity and Change in the Practices, Styles, Norms and Values of Photojournalism
This chapter deals with the impact of new digital technologies and new social practices of photographic production and circulation in the field of professional photojournalism since the early 2000s. Focusing on shifting practices, styles, norms, and values, it highlights elements of both continuity and change with the previous analogical age. In particular, it offers an analysis of three major changes: i) the rise of so-called citizen photojournalism, i.e. the possibility for ordinary people to produce photographs that come to be valued and circulated by news organizations; ii) the increasing implementation of digital post-production, i.e. the possibility to digitally retouch or enhance a photo before circulating it, that can consecrate specific aesthetic conventions yet generating considerable controversy in terms of standards and norms; iii) the symbolic struggle for distinction and authorship among top international photojournalists, as an effect of the emergence of non-professional producers and new digital technologies of production and post-production. In the end, the chapter outlines a problematization of the increasingly diffused discoursive transition from the value of \u201cobjectivity\u201d to the value of \u201ctrustworthiness\u201d within professional photojournalism. As a whole, it urges for more empirical investigations on socially situated practices of digital production as well as on existing institutional frameworks