Department of Chemistry, University of Helsinki, Finland, P.O. Box 55, Helsinki FI-00014, Finland.
School of Pharmacy, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, Finland.
Mol Pharm. 2023 Jun 5;20(6):3127-3139. doi: 10.1021/acs.molpharmaceut.3c00119. Epub 2023 May 3.
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.
硼中子俘获治疗（BNCT）是一种癌症治疗方法，其中硼传递剂起着至关重要的作用。理论上，具有高肿瘤靶向能力的传递剂可以选择性地消除肿瘤细胞，而不会引起有害的副作用。我们多年来一直在研究 GLUT1 靶向 BNCT 的策略，并发现了多种有前途的命中化合物，这些化合物在体外的表现优于临床应用的硼传递剂。在此，我们通过进一步多样化碳水化合物支架，以绘制碳水化合物核心的最佳立体化学，继续在该领域开展工作。在糖的立体异构体的甜蜜斗争中，合成了带有硼烷的 D-半乳糖、D-甘露糖和 D-阿洛糖，并进行了体外分析研究——早期的 D-葡萄糖研究工作作为参考。我们发现，所有单糖传递剂在体外的硼传递能力都明显优于临床批准使用的传递剂，从而为推进体内临床前评估研究奠定了坚实的基础。
