The DSpace digital repository system captures, stores, indexes, preserves, and distributes digital research material. http://http://dspace.unitus.it:80 2013-05-23T05:59:46Z 2013-05-23T05:59:46Z Saladino, Raffaele Barontini, Maurizio Crucianelli, Marcello Nencioni, Lucia Sgarbanti, Rossella Palamara, Anna Teresa http://hdl.handle.net/2067/1798 2011-06-28T15:21:15Z 2009-12-31T23:00:00Z

Title: Current advances in anti-influenza therapy Authors: Saladino, Raffaele; Barontini, Maurizio; Crucianelli, Marcello; Nencioni, Lucia; Sgarbanti, Rossella; Palamara, Anna Teresa Abstract: Every year, influenza epidemics cause numerous deaths and millions of hospitalizations, but the most frightening effects are seen when new strains of the virus emerge from different species (e.g. the swine-origin influenza A/H1N1 virus), causing world-wide outbreaks of infection. Several antiviral compounds have been developed against influenza virus to interfere with specific events in the replication cycle. Among them, the inhibitors of viral uncoating (amantadine), nucleoside inhibitors (ribavirin), viral transcription and neuraminidase inhibitors (zanamivir and oseltamivir) are reported as examples of traditional virus-based antiviral strategies. However, for most of them the efficacy is often limited by toxicity and the almost inevitable selection of drug-resistant viral mutants. Thus, the discovery of novel anti-influenza drugs that target general cell signaling pathways essential for viral replication, irrespective to the specific origin of the virus, would decrease the emergence of drug resistance and increase the effectiveness towards different strains of influenza virus. In this context, virus-activated intracellular cascades, finely regulated by small changes in the intracellular redox state, can contribute to inhibit influenza virus replication and pathogenesis of virus-induced disease. This novel therapeutic approach involves advanced cell-based antiviral strategies. In this review current advances in the anti-influenza therapy for both traditional virus-based antiviral strategies as well as for alternative cell-based antiviral strategies are described focusing on the last 10 years. Anti-influenza compounds are classified on the basis of their chemical structure with a special attention to describe their synthetic pathways and the corresponding structure activity relationships.

2009-12-31T23:00:00Z Bernini, Roberta Barontini, Maurizio Spatafora, Carmela http://hdl.handle.net/2067/1734 2011-06-30T14:20:14Z 2008-12-31T23:00:00Z

Title: New lipophilic piceatannol derivatives exhibiting antioxidant activity prepared by aromatic hydroxylation with 2-iodoxybenzoic acid (IBX) Authors: Bernini, Roberta; Barontini, Maurizio; Spatafora, Carmela Abstract: Piceatannol (E-3,5,3’,4’ tetrahydroxystilbene) is a phytoalexin synthesized in grapes in response to stress conditions. It exhibits strong antioxidant and antileukaemic activities due to the presence of the catechol moiety. To modify some physical properties like solubility, and miscibility in non-aqueous media some new previously unreported piceatannol derivatives having lipophilic chains on the A-ring were prepared in good yields by a simple and efficient procedure. The key step was a chemo- and regioselective aromatic hydroxylation with 2-iodoxybenzoic acid (IBX). The new compounds showed antioxidant activity and seemed promising for possible applications as multifunctional emulsifiers in food, cosmetic and pharmaceutical fields. Description: L'articolo è disponibile sul sito dell'editore: http://www.mdpi.com

2008-12-31T23:00:00Z Barontini, Maurizio Crisante, Fernanda Fabrizi, Giancarlo Mincione, Enrico http://hdl.handle.net/2067/1572 2011-06-30T13:18:48Z 2009-12-31T23:00:00Z

Title: New and efficient syntheses of hydroxytyrosol and its lipophilic derivatives Authors: Barontini, Maurizio; Crisante, Fernanda; Fabrizi, Giancarlo; Mincione, Enrico Abstract: New and efficient oxidative procedures to synthesize hydroxytyrosol and its lipophilic derivatives are described. Starting materials are available and natural compounds such as tyrosol and homovanillyl alcohol. The oxidants of choice are both homogeneous and heterogeneous 2-iodoxybenzoic acid (IBX and IBX-polystyrene) able to perform the aromatic hydroxylation and the oxidative demethylation of phenolic compounds with a chemo and regioselectivity similar to that of the polyphenol oxidase and cytochrome P450. The reactions proceed quickly and the final products are isolated in good yields and high purity. After the first oxidation, IBX-polystyrene is recovered by simple filtration, regenerated and reused for more cycles of oxidation reactions without loss of efficiency

2009-12-31T23:00:00Z Bernini, Roberta Mincione, Enrico Barontini, Maurizio Crisante, Fernanda Fabrizi, Giancarlo Gambacorta, Augusto http://hdl.handle.net/2067/1879 2011-06-29T14:21:07Z 2006-12-31T23:00:00Z

Title: Dimethyl carbonate: an environmentally friendly solvent for hydrogen peroxide (H2O2)/methyltrioxorhenium (CH3ReO3, MTO) catalytic oxidations Authors: Bernini, Roberta; Mincione, Enrico; Barontini, Maurizio; Crisante, Fernanda; Fabrizi, Giancarlo; Gambacorta, Augusto Abstract: Environmentally friendly oxidations of various organic compounds with the hydrogen peroxide (H2O2)/methyltrioxorhenium(CH3ReO3, MTO) catalytic system have been described in dimethyl carbonate (DMC), a cheap commercially available and benign chemical having interesting solvating properties, low toxicity and high biodegradability. Oxidations proceeded with good conversions and in good yields. Spectrophotometric analysis demonstrated that the [CH3ReO(O–O)2] complex was formed in DMC and that it was stable for several days at room temperature. Description: L'articolo è disponibile sul sito dell'editore: http://www.sciencedirect.com

2006-12-31T23:00:00Z Bernini, Roberta Mincione, Enrico Crisante, Fernanda Barontini, Maurizio Fabrizi, Giancarlo Gentili, Patrizia http://hdl.handle.net/2067/1881 2011-06-28T13:21:08Z 2006-12-31T23:00:00Z

Title: Chemoselective and efficient carboxymethylation of the alcoholic chain of phenols by dimethyl carbonate (DMC). Authors: Bernini, Roberta; Mincione, Enrico; Crisante, Fernanda; Barontini, Maurizio; Fabrizi, Giancarlo; Gentili, Patrizia Abstract: The efficiency of dimethyl carbonate (DMC) as chemoselective carbomethoxylating agent of the alcoholic chain of phenols has been investigated. In the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or sulfuric acid as catalysts. New carbomethoxylated phenolic compounds were obtained in quantitative yields. A new efficient derivatization of the aliphatic alcoholic chain of the precious natural hydroxytyrosol is described, which increases the lipophilicity of the hydroxytyrosol. The antioxidant activity of this new carboxymethylated hydroxytyrosol 8 has been investigated using DPPH radical scavenging test. The results showed that this new compound has an antioxidant activity similar to hydroxytyrosol. Description: L'articolo è disponibile sul sito dell'editore: http://www.sciencedirect.com

2006-12-31T23:00:00Z Barontini, Maurizio http://hdl.handle.net/2067/1983 2011-04-22T00:31:44Z 2008-04-21T22:00:00Z

Title: Nuove metodologie sintetiche di green chemistry per l’ottenimento di prodotti Authors: Barontini, Maurizio Abstract: L’attività di ricerca svolta in questo dottorato si è basata sullo sviluppo e sull’applicazione di nuove metodologie sintetiche innovative ed ecocompatibili, nel rispetto di alcuni principi della green chemistry. In particolare, nella prima parte del lavoro, è stata estesa l’applicabilità del sistema catalitico acqua ossigenata (H2O2)/metiltriossorenio (CH3ReO3, MTO) in solventi innovativi a basso impatto ambientale, quali il liquido ionico [bmim(BF4)] e il dimetil carbonato (DMC) per condurre ossidazioni catalitiche di un cospicuo numero di sostanze organiche. I buoni risultati ottenuti hanno evidenziato che tale sistema ossidante ha mantenuto la sua efficienza e versatilità in entrambi i solventi. Tuttavia in generale, l’utilizzo del DMC è risultato più vantaggioso rispetto al liquido ionico per una serie di fattori, quali la bassa tossicità, la maggiore disponibilità commerciale, il minor costo, la maggiore reattività e versatilità del sistema ossidativo; la maggiore facilità di lavorazione. Di particolare interesse sono risultati i chinoni alchilati ottenuti dall’ossidazione catalitica dei corrispondenti fenoli, in quanto hanno mostrato una buona attività antifungina verso un discreto numero di specie contaminanti il suolo ed alimenti, che in alcuni casi è risultata anche superiore a quella di un antifungino commerciale, preso come riferimento. Successivamente, con l’obiettivo di condurre processi a basso impatto ambientale e di recuperare e valorizzare alcuni dei componenti fenolici presenti nei reflui agroindustriali, è stata sviluppata una sintesi di 4-vinil fenoli a partire dagli acidi cinnamici, utilizzando le microonde senza ricorrere all’utilizzo dei solventi organici. Le condizioni sperimentali ottimizzate hanno permesso di ottenere le molecole target in tempi brevi e in buone rese. Tale metodologia è stata estesa anche a campioni di acido ferulico provenienti da estratti naturali di crusca, dimostrando la sua validità anche su matrici vegetali. La ricerca è successivamente proseguita con l’obiettivo di utilizzare acidi cinnamici e tirosolo per la sintesi di molecole ad alto valore aggiunto, quali le 4-aril-3,4-diidrocumarine. Di particolare interesse sono risultati anche i prodotti derivanti dall’apertura idrolitica dell’anello lattonico, in quanto hanno mostrato un’attività antiossidante superiore a quella del tirosolo. Nel corso di queste sintesi si è reso necessario lo sviluppo di nuove metodologie di protezione selettiva di funzioni alcoliche presenti nelle molecole fenoliche utilizzate. In particolare, sono state messe a punto nuove metodologie di: 1. carbossimetilazione, utilizzando il DMC come solvente e reagente; 2. trifluoroacetilazione con acido trifluoroacetico; 3. acetilazione, utilizzando acetonitrile/acido cloridrico oppure cloruro di acetile/DMC; 4. esterificazione con cloruri degli acidi a catena lunga, satura ed insatura. Oltre alla metodologia di protezione, sono risultati interessanti anche i prodotti ottenuti, in quanto molecole antiossidanti dotate di una maggiore lipofilicità e quindi maggiore biodisponibilità rispetto a quelle naturali. Fra i risultati ottenuti in questa tesi di dottorato, di particolare interesse è stato il lavoro svolto per la messa a punto di due nuove procedure sintetiche dell’idrossitirosolo, una molecola dotata di molteplici attività biologiche, a partire da materiali di partenza presenti negli scarti agroindustriali, quali il tirosolo e l’alcol omovanillico e l’utilizzazione di alcuni rettivi dello iodio ipervalente (IBX, DMP). Tali procedure, per la loro originalità, semplicità, economicità, efficienza e il loro basso impatto ambientale, sono state oggetto di due brevetti nazionali depositati e sono promettenti per applicazioni a livello industriale.; The research activity of this PhD course has been based on the development of innovative and environmentally friendly synthetic methodologies using natural compounds as starting materials and applying some principles of green chemistry. In particular, a first aim has been the applicability of the hydrogen peroxide (H2O2)/methyltrioxorhenium (CH3ReO3, MTO) catalytic system in ecofriendly solvents such as ionic liquid [bmim(BF4)] and dimethyl carbonate (DMC) to perform the oxidative modifications of a wide number of organic compounds. The obtained results showed that the above-cited oxidant system maintained its efficiency and versatility in both solvents. Nevertheless, the use of DMC resulted more convenient than ionic liquid for the following factors: low toxicity, more availability, low cost, more reactivity and versatility of the oxidant system, more easy manipulation. Between oxidized compounds, some p-benzoquinones deriving from the catalytic oxidation of phenols resulted interesting for their tested antifungal activity against a wide number of fungi widespread in soil and food. In some cases, they resulted more active than a commercial antifungal agent (ketoconazole). Subsequently, in order to perform ecofriendly processes using phenolic components present in agroindustrial wastes, a new decarboxylation-microwave assisted of cinnamic acids to get 4-vinyl phenols have been developed. The experimental conditions have been optimized to obtain the target molecule in satisfactory yield. Such methodology has been also extended to samples of ferulic acid deriving from natural extract of flecks. This experiment demonstrated the applicability of this methodology on vegetal matrix. The research has been continued using cinnamic acids and tyrosol as starting materials for the synthesis of 4-aryl-3,4-dihydrocumarins, high add value-molecules. The corresponding products deriving from the hydrolytic opening of the lactonic ring have been tested as antioxidants and showed an higher activity than tyrosol. To achieve these syntheses, new methodologies of selective protection of alcoholic functions present in phenolic compounds have been optimized: 1. carbomethoxylation, using the DMC as solvent as well as reagent; 2. trifluoroacetylation with trifluoroacetic acid; 3. acetylation, using acetonitrile/chloridric acid or acetyl chloride /DMC; 4. esterification with acyl chlorides having long saturated and unsaturated chains. The obtained products were lipophilic antioxidants more bioavailable than natural antioxidants. Two new synthetic procedures of bioactive hydroxytyrosol have been developed. Tyrosol and homovanillyl alcohol have been used as starting materials and some hypervalent iodine reagents (IBX, DMP) as reagents. Such procedures, for their originality, simplicity, economic validity, efficiency and low environmental impact, have been object of two national patents and are promising for industrial applications. Description: Dottorato di ricerca in Scienze ambientali

2008-04-21T22:00:00Z Bernini, Roberta Barontini, Maurizio Mosesso, Pasquale Pepe, Gaetano Willfoer, Stefan M. Sjoeholm, Rainer E. Eklund, Patrick C. Saladino, Raffaele http://hdl.handle.net/2067/1347 2011-06-30T15:51:30Z 2008-12-31T23:00:00Z

Title: A selective de-O-methylation of guaiacyl lignans to corresponding catechol derivatives by 2-iodoxybenzoic acid (IBX). The role of the catechol moiety on the toxicity of lignans Authors: Bernini, Roberta; Barontini, Maurizio; Mosesso, Pasquale; Pepe, Gaetano; Willfoer, Stefan M.; Sjoeholm, Rainer E.; Eklund, Patrick C.; Saladino, Raffaele Abstract: We report here the first selective de-O-methylation of a large panel of guaiacyl lignans to the corresponding catechol derivatives by using IBX as primary oxidant under green conditions (dimethyl carbonate–H2O solvent) through an in situ reduction procedure. The influence of the catechol moiety on the cytotoxicity and genotoxicity of new lignan derivatives has been investigated. The results obtained indicated that the presence of the catechol moiety sharply enhances the clastogenic potential (e.g. induction of chromosomal aberrations), the cytotoxicity and the modulation of cell cycle progression with respect to the parent compounds. Thus, despite the in vitro antioxidant activity usually described for catechol derivatives, our results show for the first time the generation of a clastogenic potential, highly indicative of a long-term genetic and cancer risk Description: L'articolo è disponibile sul sito dell'editore: http://www.rsc.org

2008-12-31T23:00:00Z