• tumour metabolism
• cancer hypoxia
• hLDH5
• glycoconjugates

Most invasive tumor phenotypes are characterized by a metabolic switch to an increased rate of glycolysis even under normoxic conditions, which is called “aerobic glycolysis” or “Warburg effect”. Although mitochondrial respiration is much more efficient in terms of ATP yield per moles of glucose than aerobic glycolysis, the latter confers a growth advantage to cancer cells, in addition to a higher uptake of glucose, especially in hypoxic environments.

The evolution towards more aggressive phenotypes with metastatic potential is promoted by hypoxia, as well as the acquisition of a stem-like state, thus increasing chances of cancer relapse. Moreover, gene expression for certain key enzymes is enhanced, such as the muscle isoform of lactate dehydrogenase (LDH5), which could be a potential target for cancer therapy.

Synthesis of small organic molecules as inhibitors of human lactate dehydrogenase isoform 5 has been the topic of the present work.