During my Phd I have been working on the developement of small molecules as modulators of epigenetic and non-epigenetic targets involved in cancer development ad progression. Mainly my work have been focused on the development of inhibitors (dimethylpyridone containing pyrrole- and pyrazole-based) of the lysine methyltransferase EZH2 as the catalytically active member of the Polycomb complex PRC2. These studies yielded the identification of novel EZH2is, also revealing nice SAR data. Some of the novel compounds showed promising activity in cancer cells having antiproliferative effects, reducing the H3K27 methylation, inducing apoptosis and autophagy. One of the novel compounds proved active also in a mouse model of medulloblastoma. Additionally, a Medicinal Chemistry study on Astemizole, as potential PRC2 disruptor, have been performed. For this project no biological data are jet available. In addition, a guest research stay at the University of Oxford (with S. Conway) resulted in a study on the design, synthesis and preliminary assays of photoaffinity probes for BET bromodomains. Finally, I worked on a new target from the field of lipid signalling, alkylglycerone phosphate synthase (AGPS) by developing SAR studied on the first in class AGPS inhibitor published in 2015 by the group of Prof. Mai.
|Titolo:||From epigenetics to lipid metabolism: different approaches to fight cancer|
|Data di discussione:||12-feb-2018|
|Appartiene alla tipologia:||07a Tesi di Dottorato|