N-乙酰基-12-氨基亚甲基-14-脱氧穿心莲内酯衍生物的合成及其抗肿瘤活性

Synthesis and Antitumor Activity of N-Acetyl-12-aminomethyl-14-deoxy Andrographolide Derivatives

目的:设计和合成出新的穿心莲内酯衍生物并研究其抗肿瘤活性。方法:以穿心莲内酯(1)为原料,在醇钠作用下,和硝基甲烷发生Michael加成反应脱水生成12-硝基甲基-14-脱氧穿心莲内酯(2),再在醋酐的保护下在铁粉醋酸中还原生成N-乙酰基-12-氨基亚甲基-14-脱氧穿心莲内酯(3),然后再与酸在DCC、DMAP作用下酯化生成目标化合物。按MTT方法测定了目标化合物的抗肿瘤活性。结果和结论:合成了未见文献报道的10个穿心莲内酯衍生物(4a^4j),其结构经核磁、质谱和元素分析等数据确证。初步的抗肿瘤活性研究表明:10个目标化合物均具有不同程度的抗肿瘤活性;其中化合物4c对人肝细胞肝癌SMMC-7721的抑制百分率超过穿心莲内酯。

AIM： To study the synthesis and antitumor activity of the andrographolide derivatives. METHODS： Michael addition, reduction and esterification were used in the synthesis of the title compounds. The antitumor growth inhibition percentage was measured based on MTT method. RESULTS AND CONCLUSION ： Ten compounds of N- acetyl-12-aminomethyl-14-deoxy andrographolide derivatives （4a- 4j） synthesized, their structures were identified by^1 NMR, MS and elementary analysis, and the preliminary antitumor activity research showed that all of the compounds had different activities, and compound 4c had stronger activity to liver cancer than that of andrographolide.