Muz Barbara, Azab Abdel Kareem, Confalonieri Laura, Del Grosso Erika, Fallarini Silvia, Imperio Daniela, Panza Luigi
Department of Radiation Oncology, Cancer Biology Division, Washington University in St. Louis, School of Medicine, 4511 Forest Park Ave, Room 3103, St. Louis, MO 63108, United States.
Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, L.go Donegani 2, Novara 28100, Italy.
Bioorg Med Chem. 2022 Apr 1;59:116659. doi: 10.1016/j.bmc.2022.116659. Epub 2022 Feb 19.
The synthesis of d-glucoheptose derivative containing a boronic moiety is described herein. Starting from benzyl 6,7-dideoxy-2,3,4-tri-O-benzyl-β-d-gluco-ept-6-enopyranoside, the introduction of the boronic acid was performed through a metathesis reaction by using MIDA vinyl boronic acid and the 2nd generation Grubbs catalyst. Hydrogenation led to the final product in only two reaction steps. This new sugar-containing boronic acid in the skeleton could mimic carbohydrate behavior and follow the glucose uptake in living cells. The in vitro toxicity tests performed in fibroblasts and glioma tumor cell lines showed minimal toxicity. Boron uptake measured using ICP-MS was minimal in fibroblasts, while in glioma cells showed a value of 6 ng of total boron accumulation per mg of cells, implying that compound 1a is able to accumulate selectively in the tumor tissues compared to normal.
本文描述了含硼酸部分的d-葡庚糖衍生物的合成。从苄基6,7-二脱氧-2,3,4-三-O-苄基-β-d-葡庚-6-烯吡喃糖苷开始，通过使用MIDA乙烯基硼酸和第二代格拉布催化剂的复分解反应引入硼酸。氢化反应仅通过两个反应步骤就得到了最终产物。这种骨架中含新型硼酸的糖能够模拟碳水化合物的行为，并在活细胞中呈现葡萄糖摄取情况。在成纤维细胞和胶质瘤肿瘤细胞系中进行的体外毒性测试显示毒性极小。使用电感耦合等离子体质谱法测量的硼摄取量在成纤维细胞中极小，而在胶质瘤细胞中显示每毫克细胞有6纳克的总硼积累，这意味着与正常组织相比，化合物1a能够选择性地在肿瘤组织中积累。
