【摘要】 合成了13个新的鬼臼毒素衍生物5-17，经元素分析、IR、MS、ESR和1HNMR分析确证了其组成和结构，并对它们进行了抑制小鼠淋巴白血病P388和人胃腺癌SGC-7901细胞的体外筛选．发现新化合物5、7－10对两种瘤株均有显著抑制活性，4’－O-去甲基鬼臼毒素5、10-13的抗癌活性大于相应的4’-甲氧基类似物6、14－17，用“－O－”桥取代C－4位的“－NH－”桥可导致抗癌活性降低．更多还原

【Abstract】 Thirteen new 4β-substituted podophyllotoxin derivatives 5-17 were synthesizedand their structures were confirmed by IR, MS, 1H NMR and ESR as well as elementaryanalysis. All new compounds were evaluated for their anticancer activity against mouseleukemia P388 and human stomach carcinoma SGC-7901 cells in vitro- Compounds 5, 7-10exhibited a remarkable inhibition activity against both P388 and SGC-7901 cells. In a struc-ture-activity comparison it was found that 4’ -O-demethylpodophyllotoxins 5, 10-13 showeda superior activity to the corresponding 4’ -methoxy analogues 6, 14-17 lacking a free OHgroup at C-4’. The replacement of the "-NH-" bridge at C-4 with the "-O-" bridge re-sulted in lowering of the anticancer activity. These results demonstrate the possibility ofconsiderable simplification in the sugar structure of VP-16 and the importance of 4’ -phenolichydroxyl group, and suggest further elaboration of 4β-nitrogen-containing substitutlent tooptimize the structure of this class of anticancer compounds.更多还原