Alberta Ingenuity Centre for Carbohydrate Science and Department of Chemistry, The University of Alberta, Gunning-Lemieux Chemistry Centre, Edmonton, Canada AB T6G 2G2.
Bioorg Med Chem Lett. 2011 Sep 1;21(17):5107-12. doi: 10.1016/S0960-894X(11)01095-X.
In previous studies, we have identified a family of benzo[b]furan and benzo[b]thiophene derivatives linked to amino sugars (1-6) that are cytotoxic to a range of cancer cell lines. We describe here an exploration of the effect of structural modification of the amino group on one of the carbohydrate residues (4-amino-2,3,4,6-tetradeoxy-α-l-threo-hexopyranoside) on in vitro cytotoxicity. It has been found that maintaining at least one basic functional group around the C-4 position in the carbohydrate moiety is crucial for cytotoxicity. Furthermore, it appears that modifications around the C-4 position are limited by suitable hydrophilic/hydrophobic and/or ionic interactions, as well as steric constraints.
在以前的研究中，我们已经确定了一系列与氨基糖（1-6）相连的苯并[b]呋喃和苯并[b]噻吩衍生物，它们对多种癌细胞系具有细胞毒性。在这里，我们描述了对碳水化合物残基（4-氨基-2,3,4,6-四脱氧-α-l-苏式-己吡喃糖苷）上氨基的结构修饰对体外细胞毒性的影响的探索。已经发现，在碳水化合物部分的 C-4 位置周围保持至少一个碱性官能团对于细胞毒性至关重要。此外，似乎 C-4 位置周围的修饰受到合适的亲水性/疏水性和/或离子相互作用以及空间位阻的限制。
