Design, synthesis and biological evaluation of boronic acid-containing quinoxaline derivatives as potential boron carriers for boron neutron capture therapy

Boron neutron capture therapy (BNCT) is limited by insufficient tumor selective boron delivery. In this study, a series of boronic acid-containing quinoxaline derivatives were designed and synthesized as potential boron carriers. Molecular docking suggested that compound 3 exhibited the highest binding affinity among the tested compounds. Physicochemical property prediction indicated that structural modification influenced lipophilicity and membrane permeability. Compounds 2 and 3 showed low intrinsic cytotoxicity in MDA-MB-231 and HepG2 cells, while exhibiting higher cellular boron uptake than ʟ-BPA. In MDA-MB-231 cells, boron accumulation reached 263.14 and 375.21 ng/10⁷ cells for compounds 2 and 3, respectively, compared with 187.47 ng/10⁷ cells for ʟ-BPA; in HepG2 cells, corresponding values were 183.21 and 193.24 ng/10⁷ cells, respectively, versus 145.55 ng/10⁷ cells for ʟ-BPA. In vivo biodistribution studies further demonstrated that compound 3 achieved higher tumor boron accumulation and more favorable tumor-to-blood and tumor-to-muscle ratios compared with compound 2 and ʟ-BPA at selected time points. Overall, these findings suggest that boronic acid-containing quinoxaline derivatives represent a promising scaffold for improving boron delivery efficiency in BNCT.