Increased dependence on glucose is one of the hallmarks of cancer cells to meet their high rate of proliferation. Glucose uptake transporters (GLUTs) as transmembrane proteins facilitate the transport of glucose into cells playing a key role in tumor cells' survival. Being overexpressed in many cancer cells, make GLUTs promising therapeutic targets in cancer research. The focus of the current study is on the design and synthesis of novel molecular frameworks to investigate the impact of structural rigidity on inhibitory activities exhibited by DRB-18 as our current lead GLUT inhibitor. We performed our aimed transformation through restricting rotation of single bond linkages between the core compartment and the pendant rings resulting in a bicyclic fused ring moiety with limited possible conformations while interacting with the target protein. Finally, compounds’ inhibitory properties were measured via Glucose uptake as well as cell viability/proliferation assays in human cancer cell lines. These series of molecules have been proposed to pave the way toward developing GLUT inhibitors with higher physiological stability and improved anticancer efficacy.

Design and synthesis of small-molecule inhibitors of glucose uptake transporters as potential anticancer agents

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.