新型青蒿砜-哌嗪-磺酰胺类衍生物的合成及抗癌活性

Synthesis and Anti-tumor Activities of Novel Artemisone-piperazine-sulfonamide Derivatives

以双氢青蒿素为起始原料,经胺化、氧化、烷基化、胺化和酰化反应,快速、高效地合成了青蒿砜及其衍生物,并对所有化合物进行了结构确定.采用四甲基偶氮唑盐比色法(MTT法)研究了该类化合物对人肝癌细胞株SMMC-7721的细胞毒活性,初步研究结果表明,该类化合物具有明显的抑制人肝癌细胞增殖、诱导其凋亡的细胞活性,给药72h,半抑制浓度IC50最优值为0.09μmol/mL.

A series of artemisone derivatives was prepared from dihydroartemisinin through a seven-step conversion,which included the amination of dihydroartemisinin with thiomorpholine,the oxidation of thiomorpholine（2） with hydrogen peroxide,the alkylation of sulfone（3） with the silyl protected 4-iodobutan-1-ol,the desilylation of artemisone derivative（4）,the conversion of alcohol（5） to iodide（6）,the amination of iodide（6） with piperazine,and the sulfonylation of compound 7 with a wide arrange of sulfonyl chlorides to the desired artemisone derivatives（8）.All the new compounds were identified by NMR spectra,IR and HRMS technology.The anti-tumor activities of artemisone derivatives against human hepatoma SMMC-7721 cell lines were evaluated by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） method.It was found that these new artemisone-piperazine-sulfonamide derivatives could inhibit the proliferation of the liver cancer cell by inducing apoptosis,and the lowest IC50 value of the treatment for 72h was 0.09μmol/mL.