ETD system

Electronic theses and dissertations repository

 

Tesi etd-12212016-172138


Thesis type
Tesi di dottorato di ricerca
Author
COVIELLO, VITO
URN
etd-12212016-172138
Title
Design, synthesis and functional evaluation of novel heterocyclic compounds as drug candidates for the treatment of solid tumors
Settore scientifico disciplinare
CHIM/08
Corso di studi
SCIENZA DEL FARMACO E DELLE SOSTANZE BIOATTIVE
Commissione
tutor Prof.ssa La Motta, Concettina
Parole chiave
  • solid tumors
  • heterocyclic compounds
  • drug candidates
  • tumor
Data inizio appello
26/01/2017;
Consultabilità
parziale
Data di rilascio
26/01/2020
Riassunto analitico
In my doctoral work, I have been concerned to identify new targets involved in solid tumors. That because, all solid tumors represent more than 50% of causes of death. There are several therapeutic approaches for the treatment of these tumors, chemotherapy has identified a number of targets you can hit to fight.<br>In this thesis I show the use of small molecule as inhibitor of 3 different target for the therapy of solid tumor.<br>1. Inhibition of Protein kinases interested in the growth and tumor vascularization (EGFR and VGFR).<br>2. Three novel series of 1,2-benzisothiazole derivatives have been developed as inhibitors of carbonic anhydrase isoform IX to attack the hypoxic part of the solid tumor.<br>3. Finally, a new frontier are stem cells; glioma stem-like cells (GSC) with tumor initiating activity the cellular hierarchy in glioblastoma (GBM) and engender therapeutic resistance. In this work, I show that the FOXD1-ALDH1A3 signaling axis as a determinant of the GSC. Mechanistically, FOXD1 regulates the transcriptional activity of ALDH1A3, an established functional marker for GSC. In clinical specimens of high-grade glioma, the levels of expression of both FOXD1 and ALDH1A3 are inversely correlated with patient prognosis. A novel small molecule inhibitor of ALDH we developed, termed GA11, displays potent in vivo efficacy. Later, starting from GA11, I synthetized the series of compounds to make a structure activity relationship.
Note
La tesi in oggetto non è stata inserita correttamente nel data base dall’autore. L’autore stesso ed i relatori sono stati avvertiti di tale omissione.
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