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Tesi etd-06302014-102136


Thesis type
Tesi di laurea magistrale LM5
Author
GADO, FRANCESCA
URN
etd-06302014-102136
Title
Synthesis of indole-based inhibitors of lactate dehydrogenase
Struttura
FARMACIA
Corso di studi
CHIMICA E TECNOLOGIA FARMACEUTICHE
Commissione
relatore Prof. Minutolo, Filippo
relatore Dott.ssa Rani, Reshma
Parole chiave
  • Warburg effect
  • LDH inhibitors
  • indole
  • anticancer agents
Data inizio appello
16/07/2014;
Consultabilità
completa
Riassunto analitico
The two processes used by cells to produce energy are glycolysis and oxidative phosphorylation (OXPHOS). In hypoxic conditions OXPHOS cannot take place because oxygen is missing. Consequently, cells switch into an aerobic metabolism in which they use glycolysis to produce ATP. It was observed that cancer cells do not use OXPHOS to produce energy but glycolysis also in oxygen-rich conditions (Warburg Effect or aerobic glycolysis). The reason is that cancer cells are proliferating cells so, they need a quickly production of ATP and intermediates for the synthesis of the biomass and therefore, they cannot convert all the glucose to CO2. It is possible to use this difference between healthy and cancer cells to synthesize new selective anticancer agents acting on the metabolism of malignant cells. In eukaryotic cells, lactate dehydrogenase (LDH) covers a principal role, since it is the enzyme which converts pyruvate into lactate allowing the regeneration of NAD+ important for the continuation of glycolysis. Therefore, during my thesis I synthesized differently substituted N-methylated, N-acetylated, N-sulfonylated or N-H indoles as LDH inhibitors. <br>All the synthesized compounds are under current investigation in order to assess their inhibitory effect on LDH.<br>
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