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Tesi etd-02272015-145550


Thesis type
Tesi di dottorato di ricerca
Author
SESTITO, SIMONA
URN
etd-02272015-145550
Title
Design and synthesis of new antitumor ligands
Settore scientifico disciplinare
CHIM/08
Corso di studi
FISIOPATOLOGIA CLINICA E SCIENZE DEL FARMACO
Commissione
tutor Dott.ssa Rapposelli, Simona
Parole chiave
  • Cancer Stem Cells.
  • OXIDs
  • Glioblastoma Multiforme
  • anti-cancer strategies
  • PI3K/PDK1/Akt pathway
  • PDK1/Akt inhibitors
Data inizio appello
04/03/2015;
Consultabilità
parziale
Data di rilascio
04/03/2018
Riassunto analitico
During last decade, studies on different molecular mechanism involved both in physiological and pathological events, lead researchers to identify new pharmacological targets able to disrupt key steps of oncogenesis and metastasis proliferation. In particular investigation on phosphoinositide-dependent transduction signalling disclosed the key role of PI3K/PDK1/Akt pathway in cancer progression, but also in resistance to chemotherapy, identifying this pathway as promising target for new therapeutic strategies.<br>My PhD thesis focused on the design of OXIDs, a class of potential PI3K/Akt/PDK1 inhibitors, starting from the early stage of synthesis to the biological activity. Effects of OXIDs in different cell line will be discussed and the best OXIDs have been selected for further experiments in Human Glioblastoma Multiforme (GBM) and in GBM-derived stem cells.<br>Moreover, since MP7 is the most potent PDK1 allosteric inhibitor reported in literature, new OXID-pyridon-1-yl hybrids, in which pharmacophoric groups of MP7 are linked with OXIDs scaffold, were designed and synthesised.
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