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

[Image: see text] 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 ((10)B) and thermal neutron irradiation. For successful BNCT, (10)B-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 Zn(2+) 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]aneN(4)- and [15]aneN(5)-type ligands are uptaken into cancer cells, and their complexes with intracellular metals such as Zn(2+) would induce cell death upon thermal neutron irradiation, possibly via interactions with DNA.