N-取代-β-D-葡萄糖胺衍生物的合成及抗肿瘤活性研究
Synthesis and antitumor activity of N-substituted-β-D-glucosamine derivatives
唐丽 1李凤然 1程卯生 1刘洋1
作者信息
- 1. 沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳 110016
- 折叠
摘要
目的 设计并合成具有1,2,3-三氮唑及苯磺酰胺结构的新型N-取代-β-D-葡萄糖胺化合物,评估其在体外对人碳酸酐酶Ⅸ(CA Ⅸ)的抑制活性以及对HCT116肿瘤细胞的增殖抑制活性.方法 运用基于片段的药物设计策略并结合计算机辅助药物设计,将取代的磺酰基引入氨基葡糖胺的2位氨基,构建三氮唑基团作为连接臂与磺酰胺基团相连,以期增加化合物的选择性并减少不良反应.此外,通过计算得到的LogP(cLogP)值预测化合物的亲水性.基于拓扑极性表面积(TPSA)表征膜通透性,预测化合物对膜相关CA Ⅸ的选择性.结果与结论 共合成了 17个目标化合物,其结构均经MS、1H-NMR、13C-NMR谱确证.体外活性测试结果表明,化合物 14b(IC50=18.69 µmol·L-1)和 14c(IC50=21.25 µmol·L-1)对 HCT116 细胞的抑制活性最好.
Abstract
Seventeen novel N-substituted-β-D-glucosamine derivatives that incorporate benzenesulfonamides with 1,2,3-triazole were synthesized using a bioisosterism strategy.Each derivative was evaluated in vitro for its inhibitory activity against human carbonic anhydrase Ⅸ and tumor cytotoxicity against HCT116 cell line.Moreover,the calculated LogP(cLogP)values showed that all the compounds tended to be hydrophilic.In addition,topological polar surface area(TPSA)value-based predictions highlighted the selectivity of membrane-associated CA Ⅸ.A total of 17 target compounds were synthesized,and their structures were confirmed by MS,1H-NMR and 13C-NMR spectra.In vitro activity tests showed that compounds 14b(IC50=18.69 μmol·L-1)and 14c(IC50=21.25 µmol·L-1)had the best HCT116 cell inhibitory activity.
关键词
1,2,3-三氮唑/碳酸酐酶Ⅸ/抗肿瘤/氨基葡萄糖Key words
1,2,3-triazole/CA Ⅸ/antitumor/glucosamine引用本文复制引用
出版年
2024
NETL
NSTL
万方数据