新型双氢青蒿素哌嗪-脂肪族酰胺类化合物的合成及其抗癌活性

以双氢青蒿素（DHA）为原料，与草酰氯和哌嗪经“一锅”法制得DHA哌嗪衍生物（2）； 2与脂肪族酰氯经酰化反应合成了6个新型的双氢青蒿素哌嗪-酰胺类衍生物（4a～4f），其结构经¹H NMR， ¹³C NMR，IR和HR-ESI-MS进行表征。以四甲基偶氮唑盐比色法（MTT法）初步研究了4a～4f对人肝癌细胞株SMMC-7721的抑制活性。结果表明，4a～4f显著抑制SMMC-7721的增殖，并诱导其凋亡。其中，双氢青蒿素哌嗪-氯乙酰胺（4c）的活性最好，IC₅₀为0.05 μM，优于青蒿素（IC₅₀ 0.53 μM）和DHA（IC₅₀0.52 μM）。

Synthesis and Anticancer Activities of Novel Piperazine-Aliphatic Amide Derivatives Containing Dihydroartemisinin

A piperazine-amide derivative(2) was obtained by one-pot method, using dihydroartemisinin（DHA）, oxalyl chloride and piperazine as materials. Six novel piperazine-aliphatic amide derivatives（4a～4f） were synthesized by acylation of 2 with aliphatic acyl chloride．The structures were characterized by ¹H NMR, ¹³C NMR, IR and HR-ESI-MS. The anti-cancer activities in vitro of 4a~4f against human hepatoma SMMC-7721 cell lines were investigated by MTT method. The preliminary bioassay results showed that 4a～4f inhibited the proliferation and induced the apoptosis of SMMC-7721. Especially dihydroartemisinin piperazine chlorine acetamide（4c) had the best inhibition activity against SMMC-7721 with IC₅₀ 0.05 μM, which was superior to artemisinin（IC₅₀ 0.53 μM） and DHA（IC₅₀ 0.52 μM）.