ETD

Archivio digitale delle tesi discusse presso l'Università di Pisa

Tesi etd-06222009-105301


Tipo di tesi
Tesi di laurea specialistica
Autore
GIACOMELLI, CHIARA
URN
etd-06222009-105301
Titolo
Sintesi di inibitori dell'isoforma 5 della lattato deidrogenasi umana
Dipartimento
FARMACIA
Corso di studi
CHIMICA E TECNOLOGIA FARMACEUTICHE
Relatori
Relatore Prof. Minutolo, Filippo
Relatore Dott.ssa Granchi, Carlotta
Parole chiave
  • hypoxia
  • glycolytic phenotype
  • aerobic glycolysis
  • lactate dehydrogenase A
  • tumor
  • ldh-5
Data inizio appello
16/07/2009
Consultabilità
Parziale
Data di rilascio
16/07/2049
Riassunto
Many studies have demonstrated the presence of regions at very low oxygen concentration (hypoxia) in solid tumors; so during the tumoural progression only cells that change their metabolism and switch to glycolytic phenotype survive. Although the upregulation of glycolysis is a successful adaptation to hypoxia, it also has significant negative consequences because of increased acid production, which provokes considerable decreases in local extracellular pH. The acidification of the microenvironment facilitates tumour invasion. As a consequence, the development of hypoxic areas is very closely linked to the development of a malignant and metastatic phenotype. The molecular mechanisms that underlie metabolic reprogramming of cancer cells are complex, but the activation of hypoxia-inducible factor (HIF) represents one of the principal causes of the metabolic switch. HIF-1 is a transcription factor that is activated by hypoxic stress, causing a up-regulation of GLUT1, HK1 and HK2, and lactate dehydrogenase A (LDH-A). In my thesis work I tried to synthesize molecules able to inhibit LDH-A, in fact, by inhibiting the lactic fermentation, the lack of NAD+ cofactors causes the block of glycolysis and, consequently, the interruption of energy production.
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