ETD system

Electronic theses and dissertations repository

 

Tesi etd-01072010-110815


Thesis type
Tesi di laurea specialistica
Author
DEL FIANDRA, CLAUDIA
URN
etd-01072010-110815
Title
Sintesi di inibitori eterociclici della lattato deidrogenasi umana
Struttura
FARMACIA
Corso di studi
CHIMICA E TECNOLOGIA FARMACEUTICHE
Commissione
relatore Prof. Minutolo, Filippo
correlatore Dott. Sarabindu, Roy
Parole chiave
  • tumor
  • lactate dehydrogenase A
  • aerobic glycolysis
  • glycolytic phenotype
  • hypoxia
  • LDH-5
Data inizio appello
28/01/2010;
Consultabilità
parziale
Data di rilascio
28/01/2050
Riassunto analitico
Many studies have demonstrated the presence of less oxygenated zones in locally advanced solid tumours, so during the tumour progression only cells that change their metabolism and switch to glycolytic phenotype survive. The up-regulation of glycolysis and lactic fermentation, with the contemporaneous inhibition of oxidative phosphorylation, is a successful adaptation to hypoxia.<br>Moreover the conversion of pyruvate to lactic acid has significant negative consequences because of increased acid production, which provokes a considerable decrease in local extracellular pH. The acidification of the microenvironment facilitates tumour invasion. So the development of hypoxic areas is very closely linked to the worsening of pathological conditions. The metabolic switch is principally caused by the activation of Hypoxia-Inducible Factor (HIF-1), a transcription factor activated by hypoxic stress, causing the overexpression of GLUT1, HK1 and HK2, and lactate dehydrogenase A (LDH-A). My thesis work deals with the synthesis of 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.
File