全反式维甲酸-正丁酸（丙戊酸）前体药物的设计、合成及抗肿瘤活性研究

目的合成全反式维甲酸（ATRA）的前体药物，增强ATRA对急性早幼粒白血病（APL）细胞的分化诱导作用。方法以乙二醇、对苯二酚、乙醇胺及乙二胺等为连接物，通过酯键和酰胺键将分化诱导剂ATRA与组蛋白去乙酰酶（mAC）抑制剂正丁酸、丙戊酸连接起来，形成前体药物。结果合成了13个ATRA与正丁酸或丙戊酸相连接的前体药物，化合物的结构经^1H-NMR、MS和IR确证。结论考察部分化合物对急性早幼粒细胞白血病细胞株NB4的生长抑制作用和对急性早幼粒白血病（APL）细胞分化诱导作用，初步的药理实验结果表明，ATRA与丙戊酸通过酰胺键连接时，对NB4细胞分化诱导能力显著增加。

Design, synthesis and antitumor activity of ATRA and butyric acid or valproic acid prodrugs

Aim To design and synthesize all-trans retinoic acid(ATRA) prodrug as able to induce acute promyelocytic leukemia(APL) cells differentiation.Methods According to the prodrug theory,compounds had been designed and synthesized which connect ATAR and butyric acid,valproic acid with different linkers,such as glycol,hydroquinone,through ester or amide bond.Results Thirteen new compounds were prepared,all of the compounds were confirmed by 1H-NMR,MS,and IR spect.Conclusion Comparing the antitumor activity of these compounds with ATRA in growth inhibition and differentiation induction to NB4 cells,compounds which ATAR connected which valproic acid showed more potent differentiation activities they show higher activities.