Salicylketoximes targeting glucose transporter 1 restrict energy supply to lung cancer cells

The glucose transporter GLUT1 is very frequently overexpressed in most tumor tissues because rapidly proliferating cancer cells rely mostly on glycolysis, a low-efficiency metabolic pathway necessitating a very high glucose consumption. Blocking GLUT1 is a promising anticancer strategy, thus we developed a novel class of GLUT1-inhibitors based on the 4-aryl-substituted salicylketoxime scaffold. Some of these compounds are efficient inhibitors of glucose uptake in lung cancer cells and have a noteworthy antiproliferative effect. In contrast to their 5-aryl-substituted regioisomers, the newly synthesized compounds reported herein do not display any significant binding to the estrogen receptors. The inhibition of glucose uptake in cancer cells by these compounds was further observed by fluorescence microscopy imaging using a fluorescent analog of glucose. Therefore, blocking the ability of tumor cells to take up glucose by means of these small-molecules, or by further optimized derivatives, may represent a successful approach in the development of novel anticancer drugs. Blackout in the city! Enhanced glucose uptake is a consequence of the augmented glycolysis occurring in neoplastic tissues, which warrants a sufficient amount of energy for their rapid growth. New salicylketoxime derivatives are able to "turn the lights off" in cancer cells by blocking their glucose uptake as a consequence of an inhibition of membrane transporter GLUT1.