Galloflavin (CAS 568‐80‐9): A Novel Inhibitor of Lactate Dehydrogenase

• DOI: 10.1002/cmdc.201100471
• Publication Date: 2011-11-04T10:53:36Z
• Authors: Marcella Manerba; Marina Vettraino; Luigi Fiume; Giuseppina Di Ste...; Andrea Sartini; Elisa Giacomini; Rosa Buonfiglio; Marinella Roberti; Maurizio Recanatini
• Keywords: Lactate dehydrogenase A

One of the most prominent alterations in cancer cells is their strict dependence on glycolytic pathway for ATP generation. This observation led to evaluation glycolysis inhibitors as potential anticancer agents. The inhibition lactate dehydrogenase (LDH) a promising way inhibit tumor cell glucose metabolism without affecting energetic balance normal tissues. However, success this approach depends chiefly availability that display good selectivity. We identified compound (galloflavin, CAS 568-80-9) which, contrast other human LDH, hinders both A and B isoforms enzyme. To determine mechanism action, we collected LDH-A -B data competition reactions with pyruvate or NADH evaluated results using software enzyme kinetics analysis. found galloflavin inhibits LDH by preferentially binding free enzyme, competing substrate cofactor. calculated Ki values were 5.46 μM (LDH-A) 15.06 (LDH-B). In cultured cells, blocked aerobic at micromolar concentrations, did not interfere respiration, induced death triggering apoptosis. our knowledge, is, date, only biochemical effect described galloflavin. Because commercially available, also describe herein procedure its synthesis report first full chemical characterization.