期刊
MOLECULAR PHARMACEUTICS
卷 20, 期 6, 页码 3127-3139出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.3c00119
关键词
boron neutron capture therapy; carboranes; carbohydrates; drug delivery; medicinal chemistr y
Boron neutron capture therapy (BNCT) is a cancer treatment that uses boron delivery agents to selectively eradicate tumor cells. In this study, we focus on a GLUT1-targeting strategy to BNCT and synthesize carborane-bearing D-galactose, D-mannose, and D-allose as potential delivery agents. We find that these agents exhibit significantly improved boron delivery capacity compared to clinically approved agents in vitro, laying the groundwork for future preclinical assessment studies.
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-bearing D-galactose, D-mannose, and D-allose are synthesized and subjected to in vitro profiling studies-with earlier work on D-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据