Citation: Shushan Mo, Zhaoshuo Wang, Dandan Ding, Zhengzheng Yan, Yunlu Dai, Jinchao Zhang, Huifang Liu, Tianjiao Liang, Jianfei Tong, Zhenhua Li, Xueyi Wang. The synthesis and evaluation of novel BPA derivatives for enhanced blood-brain barrier penetration and boron neutron capture therapy[J]. Chinese Chemical Letters, ;2025, 36(5): 110190. doi: 10.1016/j.cclet.2024.110190 shu

The synthesis and evaluation of novel BPA derivatives for enhanced blood-brain barrier penetration and boron neutron capture therapy

Shushan Mo ^{a, b, 1} ,
Zhaoshuo Wang ^{c, 1} ,
Dandan Ding ^a ,
Zhengzheng Yan ^a ,
Yunlu Dai ^d ,
Jinchao Zhang ^e ,
Huifang Liu ^b ,
Tianjiao Liang ^f ,
Jianfei Tong ^f ,
Zhenhua Li ^{a, *,} ,
Xueyi Wang ^{a, *,}

a.
The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan 523059, China
b.
College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding 071002, China
c.
Growth Factors, Nutrients and Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain
d.
Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China
e.
College of Chemistry & Materials Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding 071002, China
f.
Spallation Neutron Source Science Center, Dongguan 523803, China

zhenhuali@hbu.edu.cn

ixueyi@smu.edu.cn

Received Date: 28 March 2024
Revised Date: 25 June 2024
Accepted Date: 27 June 2024
Available Online: 27 June 2024

Figures(4)

Boron neutron capture therapy (BNCT) has emerged as a promising treatment for cancers, offering a unique approach to selectively target tumor cells while sparing healthy tissues. Despite its clinical utility, the widespread use of fructose-BPA (F-BPA) has been hampered by its limited ability to penetrate the blood-brain barrier (BBB) and potential risks for patients with certain complications such as diabetes, hyperuricemia, and gout, particularly with substantial dosages. Herein, a series of novel BPA derivatives were synthesized. After the primary screening, geniposide-BPA (G-BPA) and salidroside-BPA (S-BPA) exhibited high water solubility, low cytotoxicity and safe profiles for intravenous injection. Furthermore, both G-BPA and S-BPA had demonstrated superior efficacy in vitro against the 4T1 cell line compared with F-BPA. Notably, S-BPA displayed optimal BBB penetration capability, as evidenced by in vitro BBB models and glioblastoma models in vivo, surpassing all other BPA derivative candidates. Meanwhile, G-BPA also exhibited enhanced performance relative to the clinical drug F-BPA. In brief, G-BPA and S-BPA, as novel BPA derivatives, demonstrated notable safety profiles and remarkable boron delivery capabilities, thereby offering promising therapeutic options for BNCT in the clinic.
- Boron neutron capture therapy (BNCT),
- Novel BPA derivatives,
- Boron drug development,
- BBB penetration,
- Glioblastoma
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