• aerobic glycolysis
• glycolytic phenotype
• hypoxia
• lactate dehydrogenase A
• ldh-5
• tumor

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.