Potent Biological Activity of Fluorinated Derivatives of 2-Deoxy-d-Glucose in a Glioblastoma Model.

ABSTRACT:

Background

One defining feature of various aggressive cancers, including glioblastoma multiforme (GBM), is glycolysis upregulation, making its inhibition a promising therapeutic approach. One promising compound is 2-deoxy-d-glucose (2-DG), a d-glucose analog with high clinical potential due to its ability to inhibit glycolysis. Upon uptake, 2-DG is phosphorylated by hexokinase to 2-DG-6-phosphate, which inhibits hexokinase and downstream glycolytic enzymes. Unfortunately, therapeutic use of 2-DG is limited by poor pharmacokinetics, suppressing its efficacy.

Methods

To address these issues, we synthesized novel halogenated 2-DG analogs (2-FG, 2,2-diFG, 2-CG, and 2-BG) and evaluated their glycolytic inhibition in GBM cells. Our in vitro and computational studies suggest that t

SUBMITTER: Soltyka-Krajewska M 

PROVIDER: S-EPMC11504489 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature