【摘要】 目的为寻找高效低毒且作用谱广的鬼臼脂素类抗肿瘤药物,合成了20个4’-去甲基表鬼臼毒素芳香酰胺类化合物。方法以4’-去甲基表鬼臼毒素为原料,首先与氯乙腈进行取代反应,再与硫脲反应,最后与不同的取代芳香羧酸成酰胺制得目标化合物。采用MTT法测定目标化合物体外对人肺腺癌细胞A549、人肝肿瘤细胞株HepG2、人口腔癌KB细胞、L1210白血病细胞的抑制活性。结果与结论合成了20个未见文献报道的新化合物,目标化合物的结构均经~1H-NMR和MS谱确证,活性测试结果表明,大部分目标化合物均具有一定的肿瘤细胞增殖抑制活性。更多还原

【Abstract】 In order to find the novel epipodophyllotoxins antitumor drugs and reduce toxicity and side effect,twenty novel 4’-demethylepipodophyllotoxin aromatic amide derivatives were designed and synthesized.Amino groups were introduced by Ritter reaction,and different side chains were introduced by condensation reaction. All of them have been characterized by ~1 H-NMR and ESI-MS,and the effects of synthesized compounds against proliferations of A549,HepG2,KB,L1210 cells were evaluated by MTT test. The introduction of halogen in thiophene ring can increase the inhibition of A549,KB,L1210 cells; the introduction of halogen in indole ring can decrease the inhibition activity,however, the introduction of electron-donating group, such as methoxyl group can increase the inhibitory activity; carbon chain elongation can decease the inhibitory activity.更多还原