<em>N</em>-（氨基吡啶）苯甲酰胺类衍生物的合成与抗肿瘤活性

N-（氨基吡啶）苯甲酰胺类衍生物的合成与抗肿瘤活性

摘要:
为寻找具有抗肿瘤活性的新型组蛋白去乙酰化酶 (HDAC) 抑制剂, 在前期研究发现活性结构A和B的基础上, 设计合成了N-(2-氨基-4-吡啶) 苯甲酰胺类 (A类) 化合物和N-(2-氨基-3-吡啶) 苯甲酰胺类 (B类) 化合物各16个。32个目标化合物的结构经¹H NMR及HR-MS分析确证。体外抑HDACs活性研究表明, 除Ⅴ-20、Ⅴ-21外, 其余30个化合物在200 μmol·L⁻¹下均表现出一定的抑酶活性。对各肿瘤细胞株的体外抗增殖作用研究表明, 化合物Ⅴ-30、Ⅴ-31、Ⅴ-32对Hut78、Jurkat E6-1、A549、K562 及 MDA-MB-435s 5种肿瘤细胞具有良好的抑制活性。

Abstract:
To explore novel histone deacetylase (HDAC) inhibitors with anti-tumor activity, on the basis of preliminary studies, sixteen N-(2-amino-4-pyridine) benzamide derivaties (class A) and sixteen N-(2-amino-3- pyridine) benzamide derivaties (class B) were designed and prepared, and their structures were confirmed by ¹H NMR and HR-MS individually. The results showed that 30 target compounds except Ⅴ-20 and Ⅴ-21 had HDACs inhibitory activity and Ⅴ-13, Ⅴ-14, Ⅴ-16 were equal to CI-994 at 200 μmol·L^{−1 in vitro}. Compounds Ⅴ-30、Ⅴ-31 and Ⅴ-32 exhibited potent inhibitory activities on Hut78、Jurkat E6-1、A549、K562 and MDA-MB-435s.