title: Inhibition of tumor cell growth by a specific 6-phosphofructo-2-kinase inhibitor, N-bromoacetylethanolamine phosphate, and its analogues.
abstract: The high rate of glycolysis despite the presence of oxygen and mitochondria in tumor cells implies an important role for this process in cell division. The rate of glycolysis is assumed to be dependent on the cellular concentration of fructose 2,6-bisphosphate, the concentration of which in turn depends on a bifunctional enzyme and the ratio of this enzyme's 6-phosphofructo-2-kinase versus its fructose 2,6-bisphosphatase activities. To prove the hypothesis that inhibition of glycolysis in tumor cells by 6-phosphofructo-2-kinase inhibitors would cause inhibition of tumor cell proliferation, ten N-bromoacetylethanolamine phosphate analogues were designed, synthesized, and tested. They were screened for their activities against various human tumor cell lines to study the effects of inhibition of glycolysis on cell proliferation. The relationship between the structure of these compounds and their inhibitory activity on cell proliferation was also discussed. It was found that the activity of N-(2-methoxyethyl)-bromoacetamide, N-(2-ethoxyethyl)-bromoacetamide, and N-(3-methoxypropyl)-bromoacetamide was comparable to that of the positive control AraC. These three inhibitors showed in vivo anticancer effects in P388 transplant BDF1 mice.
authors: Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagasaki University, Japan.
authors: T
authors: T
authors: Hirata
authors: M
authors: M
authors: Watanabe
authors: S
authors: S
authors: Miura
authors: K
authors: K
authors: Ijichi
authors: M
authors: M
authors: Fukasawa
authors: R
authors: R
authors: Sakakibara
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000096:biosynthesis; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D025481:Phosphofructokinase-2; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D004983:Ethanolamines; D019344:Lactic Acid; C020161:N-bromoacetylethanolamine phosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); D025481:Phosphofructokinase-2