Design, Synthesis, and Biological Evaluation of Boron-Containing Macrocyclic Polyamines and Their Zinc(II) Complexes for Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT)
is a binary therapeutic method
for cancer treatment based on the use of a combination of a cancer-specific
drug containing boron-10 (10B) and thermal neutron irradiation.
For successful BNCT, 10B-containing molecules need to accumulate
specifically in cancer cells, because destructive effect of the generated
heavy particles is limited basically to boron-containing cells. Herein,
we report on the design and synthesis of boron compounds that are
functionalized with 9-, 12-, and 15-membered macrocyclic polyamines
and their Zn2+ complexes. Their cytotoxicity, intracellular
uptake activity into cancer cells and normal cells, and BNCT effect
are also reported. The experimental data suggest that mono- and/or
diprotonated forms of metal-free [12]­aneN4- and [15]­aneN5-type ligands are uptaken into cancer cells, and their complexes
with intracellular metals such as Zn2+ would induce cell
death upon thermal neutron irradiation, possibly via interactions
with DNA.