Inhibition of tumor cell growth by a specific 6-phosphofructo-2-kinase inhibitor, N-bromoacetylethanolamine phosphate, and its analogues

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 concent ration of fructose 2,6-bisphosphate, the concentration of which in turn dep ends on a bifunctional enzyme and the ratio of this enzyme's 6-phosphofruct o-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 t umor cell lines to study the effects of inhibition of glycolysis on cell pr oliferation. 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)-bromo acetamide, N-(2-ethoxye thyl)-bromoacetamide, and N-(3-methoxypropyl)-bromoacetamide was comparable to that of the positive control AraC. These three inhibitors showed in viv o anticancer effects in P388 transplant BDF1 mice.