目的 设计并合成组蛋白去乙酰化酶抑制剂（HDACi），并对其组蛋白去乙酰化酶（HDACs）抑制活性和体外抗肿瘤活性进行研究。方法 以N-Boc-对苯二胺和辛二酸酐为起始原料，反应制得7-（N-Boc-氨基）苯胺甲酰基庚酸，再通过胺醛缩合反应合成HDACi；并采用HDACs试剂盒和CCK-8试剂盒测试所合成目标化合物抑制HDACs的活性和抗肿瘤活性。结果 合成了26个新化合物，其结构均经过核磁共振氢谱和质谱进行了确证。初步的生物活性测试结果表明，所合成的目标化合物对HDACs的抑制活性均强于阳性药物伏立诺他，并对MCF-7、PC-3、HepG2、MGC-803和KB 5种肿瘤细胞有不同程度的抑制活性，其中希夫碱含有吸电子基的化合物对HDACs的抑制活性以及抗肿瘤活性强于其他衍生物。尤其是4-氰基化合物11c对HDACs展现出了最强的抑制活性，是阳性药伏立诺他的58倍；同时，化合物11c对肿瘤细胞MCF-7、PC3、MGC-803和HepG2展现出了最强的抗肿瘤活性，其抗胃癌MGC-803甚至是阳性药物伏立诺他的7.2倍。结论 希夫碱是一类重要的抗肿瘤药效团，能够提高HDACi的抗肿瘤活性，为今后发展新型、高效的HDACi提供了新的思路。

Objective To designe and synthesize hydroxamic acid histone deacetylase inhibitors(HDACi), and to investigate their HDAC inhibitory activities and anti-tumor activities in vitro. Methods N-(4-aminophenyl)-1,1-dimethylethyl ester and caprylic anhydride were used as starting materils to synthesize 8-((4-((tert-butoxycarbonyl)amino)phenyl)amino)-8-oxooctanoic acid. Then a series of HDACi were designed and synthesized by aldimine condensation. HDAC inhibitory activities of target compounds were evaluated by HDACs reagent kit, and their anti-tumor activities also were evaluated by CCK-8 assay. Results Twenty-six novel HDACi were synthesized and the structures were confirmed by ¹H-NMR and MS spectra. The preliminary biological results showed that these target compounds displayed potent against HDACs and significant anti-tumor activities on MCF-7, PC-3, HepG2, MGC-803, and KB cancer cells. And the inhibitors, which bore electron withdrawing group in schiff base unit, had more potent anti-HDACs and anti-tumor than other derivatives. Specifically, 4-cyano compound 11c exhibited most potent anti-HDACs, which was 58-fold more potent than vorinostat. Moreover, compound 11c showed the greatest potency against MCF-7, PC3, MGC-803, and HepG2, and which showed 7.2-fold more potent than vorinostat, against MGC-803.Conclusion Schiff base unit is a kind of important anti-tumor pharmacophore, which can enhance the anti-tumor activity of HDACi, and offer new mentality to develop novel and high-efficiency HDACi in the future.