丙戊酸水杨酰芳胺酯类化合物的设计合成及抗肿瘤活性.pdf

874 药学学报 Acta Pharmaceutica Sinica 20 13, 48 (6): 874 880 戊酸水杨酰芳胺酯类化合物的设计、合成及抗肿瘤活性研究 1 1* 2 1 1 明 , 李家明 , 何广卫 , 钟国琛 , 张艳春 (1. 安徽中医药大学药学院, 安徽省现代中药重点实验室, 安徽 合肥 230031; 2. 合肥医工医药有限公司, 安徽 合肥 230088) 1 摘要: 依据前药原理, 设计合成了系列具有抗肿瘤活性的水杨酰芳胺酯类化合物, 并通过MS 、H NMR 、 13C NMR 确证了目标化合物的结构。以K562 、A549 、A43 1 3 种细胞株为活性筛选对象, 利用MTT 法与 SRB 法进行初步的体外抗肿瘤活性研究。结果表明, 化合物 6h～6j 对 3 种细胞株的抑制活性均强于阳性化合物 gefitinib, 与原药对照 硝柳胺相当, 值得进一步研究。 关键词: 丙戊酸; 水杨酰芳胺; 抗肿瘤活性; 前药 中图分类号: R9 16 文献标识码: A 文章编号: 0513-4870 (20 13) 06-0874-07 Design, synthesis and antitumor activity of valproic acid salicylanilide esters 1 1* 2 1 1 YUAN Ming , LI Jia-ming , HE Guang-wei , ZHONG Guo-chen , ZHANG Yan-chun (1. Dep artment of Pharmacy, AnHui University of Chinese Medicine, AnHui Key Laboratory of Traditional Chinese Medicine, Hefei 230031, China; 2. Hefei Yigong Medicine Co., Ltd., Hefei 230088, China ) Abstract : A series of valproic acid salicylanilide esters were designed and synthesized based on the principle of prodrug. The structures of the target compounds were confirmed by MS, 1H NMR and 13C NMR. Anti-tumor activities of these compounds against K562, A549, A431cells in vitro were investigated by MTT assay and SRB assay. The results indicated that the compounds 6h 6j were found to have stronger cell growth inhibitory action t