• SINTESI DI INIBITORI DELLA LATTATO DEIDROGENASI 5

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. 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 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.