Boron neutron capture therapy (BNCT) is a cancer therapy
in which
boron delivery agents play a crucial role. In theory, delivery agents
with high tumor targeting capabilities can lead to selective eradication
of tumor cells without causing harmful side effects. We have been
working on a GLUT1-targeting strategy to BNCT for a number of years
and found multiple promising hit compounds which outperform the clinically
employed boron delivery agents in vitro. Herein, we continue our work
in the field by further diversification of the carbohydrate scaffold
in order to map the optimal stereochemistry of the carbohydrate core.
In the sweet battle of the epimers, carborane-bearingd-galactose,d-mannose, andd-allose are synthesized and subjected
to in vitro profiling studies—with earlier work ond-glucose serving as the reference. We find that all of the monosaccharide
delivery agents display a significantly improved boron delivery capacity
over the delivery agents approved for clinical use in vitro, thus
providing a sound foundation for advancing toward in vivo preclinical
assessment studies.