1,721,129 research outputs found
La réception d'André Gide dans la presse italienne (1895-1947)
No full textThis study focuses André Gide’s reception in the Italian press, starting from 1895, date of the first mention of the author’s name in a periodical, up to 1947, when he was awarded with the Nobel Prize. This long period is characterised by significant historical changes which profoundly affected the world of culture and literature in Europe and, more particularly, in Italy. Between the end of the 19th century to the second post-war period, two world conflicts, twenty years of dictatorship and a civil war led to an evolution of the Italian society, culture and literature. All these changes represent the historical background of Gide’s reception. Leading public figure and great European, Gide cultivates a preferential relationship with Italy; at first, this country is the destination of his first trips and, a short while afterward, a place of work and of dialogue with the local intelligentsia. The considerable presence of the author in the Italian newspapers and magazines reflects the importance of his works in Italy.
My work consisted in two different phases. First, the researching phase, in which I gathered articles and unpublished materials to trace Gide’s presence in the Italian cultural network. Second, the analysing phase, in which I studied the whole material from a critical perspective. The two world wars mark two periods of difficulty in the cultural contacts within Europe and determine the irreversible change of the panorama of the following years. For this reason, I decided to draw up a chronological partition, based on the evolution of the receiving country. I divided my study into three periods: the first one lasts from 1895 to the end of the First World War (1918); the second one, from 1919 to 1943, covers the interwar period and the beginning of the Second World War; the third one, is from the end of fascism (1943) to 1947. Through the analysis of the Italian articles devoted to Gide, which constitute my primary corpus, I will define the critical perspective of Italian intellectuals about the French writer. At the same time, the precise definition of the author’s historical and biographical relations with Italy will be essential to draw a panorama of cross-relations: the interest of Italian intellectuals in contemporary French literature overlaps with Gide’s interest in Italian culture and literature
In silico evaluation of human small heat shock protein HSP27: Homology modeling, mutation analyses and docking studies
No full textSmall heat-shock proteins, possessing chaperone-like activity, represented crucial proteins actively involved in maintain protein homeostasis, which act to prevent improper polypeptide aggregation and deposition of misfolded proteins. In this context, a number of mutations concerning the HspB1 protein proved to be associated with the development of several neuropathologies. Unfortunately, molecular mechanisms underlying the onset of these diseases and in particular the changes induced by the mutations in HspB1 structure, remain poorly characterized. On the other hand, more recent studies demonstrated that HspB1 overexpression leads to an overactive chaperone activity, which in turn contributes to the anticancer agent resistance. On these basis, Hsp27 could represent a good innovative target for development of novel cancer therapy. Therefore, in this work a computational study, based on the homology model of the complete Hsp27 protein and of several pathological mutant forms, was developed. Finally, the derived model was employed to perform, for the first time, docking simulations on a recently identified Hsp27 inhibitor, disclosing a new useful panorama to be exploited for the further development of new compounds
Reaction of 2-Dimethylaminomethylene-1,3-diones with Dinucleophiles. X. Synthesis of 5-Substituted Ethyl or Methyl 4-Isoxazolecarboxylates and Methyl 4-(2,2-Dimethyl-1-oxopropyl)-5-isoxazolecarboxylate
No full textReaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with hydroxylamine hydrochloride in methanol solution afforded in high yields the relative esters of 5-substituted 4-isoxazolecarboxylic acids II. These esters were hydrolyzed generally with concentrated hydrochloric acid-acetic acid mixtures to the corresponding carboxylic acids in satisfactory yields. Ethyl or methyl esters II isomerized with sodium ethoxide or methoxide, respectively, to the corresponding esters or hemiesters of 2-cyano-3-oxoalkanoic acids generally in excellent to satisfactory yields. Reaction of methyl 5,5-dimethyl-3-dimethylaminomethylene-2,4-dioxohexanoate with hydroxylamine hydrochloride afforded in moderate yield methyl 4-(2,2-dimethyl-1-oxopropyl)-5-isoxazolecarboxylate, which was converted by acid hydrolysis as above to 4-t-butyl-4-hydroxyfuro[3,4-d]isoxazol-6-(4H)-one
2-Pyridone derivatives as inotropic agents: synthesis, pharmacology and molecular modeling study
No full textToward the identification of the cardiac cGMP inhibited-phosphodiesterase catalytic site
No full textCyclic nucleotide phosphodiesterases (PDEs) comprise a complex group of enzymes; five major PDE families or
classes with distinctive properties have been identified. Among these a great deal of interest has recently been
focused on the so called cGMP-inhibited low Km cAMP phosphodiesterase (cGI PDE) or PDE III. A number of
positive inotropic agents, including the well-known milrinone, display a specific inhibition of PDE III as primary
mechanism of action. Recent studies have been carried out to develop a pharmacophore model of the PDE III
active site. We therefore performed molecular modelling and 3D-SAR studies so as to better define structural
requirements for potent and selective enzymatic inhibition. The DISCO (DIStance COmparison) strategy has been
applied on a set of compounds taken from literature and a milrinone analogue previously synthesized by us, all of
which are characterized by a marked inotropic effect but with varying degrees of enzyme selectivity. A common
pharmacophoric model was derived, validated and considered as starting point to perform a 3D-SAR study using
the GRID force field and PCA (Principal Component Analysis) with the aim of rationally designing more selective
inhibitors. This paper presents the results of this theoretical approach
3,4,5-Trisubstituted-1,2,4-4H-triazoles as WT and Y188L mutant HIV-1 non-nucleoside reverse transcriptase inhibitors: docking-based CoMFA and CoMSIA analyses.
No full text3,4,5-Trisubstituted-1,2,4-4H-triazoles (TTs)
have recently been identified as a new class of potent
non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors.
Two series of triazoles have been studied, one of which was
also screened against the Y188L mutant. A computational
strategy based on molecular docking studies followed by
comparative molecular fields analysis (CoMFA) and comparative
molecular similarity indices analysis (CoMSIA)
has been used to elucidate the atomic details of the RT/TT
interactions and to identify the most important features
impacting the TT antiretroviral activity. Two 3D-QSAR
CoMFA and CoMSIA models were derived, using the TT
pEC50 values measured against wild-type (WT) HIV-1
(model A) and the Y188L mutant form (model B),
respectively, as the dependent variable. The final model A
CoMSIA (rncv
2=0.97, rcv
2=0.89, SEE=0.314, and rpred
2=
0.82) and model B CoMSIA (rncv
2=0.91, rcv
2=0.61, SEE=
0.236, and rpred
2=0.73) analyses were more predictive. The
results allowed us to obtain useful information for the
design of new compounds with improved potency towards
WT HIV-1 or that are potentially active against the Y188L
mutant
2-Pyridone derivatives as inotropic agents: synthesis, pharmacology and molecular modeling study
No full text- …
