药学研究2026，Vol.45Issue(8)：841-850,10.DOI:10.13506/j.cnki.jpr.2026.08.001
姜黄素类似物EF24的糖基化衍生物的设计、合成与抗肿瘤活性
Design,synthesis and antitumor activity research of glycosylated derivatives of curcumin analogue EF24
摘要
Abstract
Objective EF24,a synthetic curcumin analog,exhibits promising antitumor activity but is limited by insufficient cellular selectivity and potential off-target cytotoxicity.This study aimed to modify EF24 through glycosylation and to evaluate its potential as a GLUT-mediated antitumor prodrug.Methods A series of EF24 glycosylated derivatives were synthesized by conjugating glucose and galactose moieties to the EF24 structure.The derivatives were characterized using NMR and HRMS.Their antiproliferative activities were evaluated in human colon cancer(SW480)and HCT-116)and breast cancer(MDA-MB-231 and MCF-7)cell lines,with normal human colon epithelial cells(NCM-460)used for selectivity assessment.GLUT1-mediated uptake was studied using GLUT inhibitors and competitive substrate assays.Results The results demonstrated that glycosylation did not significantly compromise the antiproliferative activity of EF24 in colon cancer cells and,in certain breast cancer models,even enhanced its inhibitory effects.Notably,the glycosylated derivatives exhibited markedly reduced cytotoxicity toward normal cells,thereby improving the selective antiproliferative activity against tumor cells.Molecular docking studies further indicated that glycosylation enhanced the binding affinity of EF24 to GLUT1,which contributed to its improved selectivity toward cancer cells.Conclusion Glycosylation is an effective strategy to optimize EF24's biological profile.The glycosylated derivatives demonstrated enhanced selectivity toward cancer cells and reduced toxicity to normal cells,making them potential candidates for GLUT-targeted antitumor prodrug development.关键词
3,5-双(2-氟苄基)哌啶-4-酮/糖基化/葡萄糖转运蛋白1/抗肿瘤活性/肿瘤细胞选择性Key words
EF24/Glycosylation/GLUT1/Antitumor activity/Tumor cell selectivity分类
医药卫生引用本文复制引用
唐春旸,傅俊杰,余海嘉,邹瑜,陈锦华..姜黄素类似物EF24的糖基化衍生物的设计、合成与抗肿瘤活性[J].药学研究,2026,45(8):841-850,10.基金项目
国家自然科学基金项目(No.22577041) （No.22577041）
湖北省教育厅科学研究计划青年人才项目(No.Q20231113) （No.Q20231113）
武汉市卫健委科研项目(No.WX23B12) （No.WX23B12）
