Sintesi di nuovi derivati tri-componente per target photodynamic therapy della neoplasia prostatica

Therapies for the treatment of prostate cancer show several limitations, especially when the cancer metastasizes or acquires resistance to treatment. In addition, most of the therapies currently used entails the occurrence of serious side effects. A different therapeutic approach, more selective and less invasive with respect either to radio or to chemotherapy, is represented by the photodynamic therapy (PDT). The PDT is a treatment that makes use of photosensitive drugs: these agents are pharmacologically inactive until they are irradiated with light at an appropriate wavelength and in the presence of oxygen. The drug, activated by light, forms singlet oxygen, a highly reactive chemical species directly responsible for DNA damage, thus of cell death. In this thesis we present two synthetic strategies for the preparation of two new tri-component derivatives for photodynamic therapy of advanced prostate cancer, namely DRPDT1 and DRPDT2. Both derivatives are formed by three basic elements covalently bounded to each other: a specific ligand with high affinity for the androgen receptor, a suitably chosen spacer molecule and a photoactivated molecule. In particular, DRPDT2 differs from DRPDT1 from the nature of the AR ligand. In fact, in the case of DRPDT2 we used a synthetically engineered androgen receptor ligand able to photo-react even in the absence of oxygen, by delivering NO radical. The presence of this additional pharmacophore, together with the porphyrin, may ensure an additive/synergistic effect to the photo-stimulated therapy, which than may act both in the presence of oxygen and in hypoxic conditions. This approach represents the first example of multimodal photodynamic therapy for prostate cancer.

Beyond simple proton transfer processes: domino reactions between 4-substituted indoles and nitroethene as a new gateway to ergot alkaloids

The multimodal biology activity of ergot alkaloids is known by humankind since middle ages. Synthetically modified ergot alkaloids are used for the treatment of various medical conditions. Despite the great progress in organic syntheses, the total synthesis of ergot alkaloids remains a great challenge due to the complexity of their polycyclic structure with multiple stereogenic centres. This project has developed a new domino reaction between indoles bearing a Michael acceptor at the 4 position and nitroethene, leading to potential ergot alkaloid precursors in highly enantioenriched form. The reaction was optimised and applied to a large variety of substrate with good results. Even if unfortunately all attempts to further modify the obtained polycyclic structure failed, it was found a reaction able to produce the diastereoisomer of the polycyclic product in excellent yields. The compounds synthetized were characterized by NMR and ESIMS analysis confirming the structure and their enantiomeric excess was determined by chiral stationary phase HPLC. The mechanism of the reaction was evaluated by DFT calculations, showing the formation of a key bicoordinated nitronate intermediate, and fully accounting for the results observed with all substrates. The relative and absolute configuration of the adducts were determined by a combination of NMR, ECD and computational methods.

Interpretazione per i media: il caso particolare delle interviste sul podio della Formula 1

This dissertation analyses the live simultaneous interpretation from English into Italian of six 2013 Formula 1 World Championship podium interviews and focuses on four main aspects: how the interpreter handled the décalage at the end of the interview and during the turn-taking; if he used any marker to indicate that he was starting to translate a new turn of the source text; what he did when overlapped speech in the source texts occurred; what happened when the Italian commentators talked during the interpreter’s translation. In the first chapter a description mainly of what a Formula 1 podium interview is and what an interpreter translates during the Formula 1 weekends is present. In the second chapter a literature review on media interpreting, with particular attention put on Straniero Sergio’s paper on translating Formula 1 press-conferences (2003), and turn-taking is provided. In the third chapter the methodology used to obtain and process the video and audio files of source and target texts and to transcribe them is described. We concentrated primarily on Thibault’s multimodal text transcription techniques (2000) and on how they were used and adapted to fit the purposes of this dissertation. In the fourth chapter the results obtained through the analysis of the source and target texts are shown and described, focusing only on the objectives of the dissertation, without aiming to provide a qualitative evaluation of the interpretations. In the fifth and last chapter the conclusions and some final remarks are made, based on the results obtained during the analysis and the hope for a more in depth knowledge of Italian Formula 1 interpreter’s working conditions.