论文部分内容阅读
目的设计合成鬼臼毒素4β-(1,3,4-噁二唑-2-氨基)衍生物,并寻求具有高效低毒抗癌活性的新化合物。方法鬼臼毒素经叠氮化、还原、加成、消除得到4β-异硫氰酸酯-4-脱氧鬼臼毒素(4),再与酰肼化合物反应得到氨基硫脲衍生物,最后经环化得到目标化合物。采用MTT法,以5-氟尿嘧啶、鬼臼毒素、VP-16为阳性对照药,评价目标化合物对人前列腺癌细胞(DU-145)、人胃癌细胞(SGC-7901)、人非小细胞肺癌细胞(A549)、神经母细胞瘤细胞(SH-SY5Y)、人肝癌细胞(HepG2)、子宫颈癌细胞(HeLa)6种肿瘤细胞以及1种正常细胞小鼠成纤维细胞(L929)的细胞毒活性。结果合成了9个新化合物,其结构经IR、1H-NMR、13C-NMR和MS确证。体外抗癌活性实验表明,目标化合物对正常细胞的毒性均远远小于阳性对照,部分化合物显示出较好的抗癌活性。结论在这一系列衍生物中,化合物6b对所测试细胞系的细胞毒活性显示了突出的生物活性。
OBJECTIVE To design and synthesize podophyllotoxin 4β- (1,3,4-oxadiazole-2-amino) derivatives and to search for new compounds with high potency and low toxicity anticancer activity. Methods Podophyllotoxin was treated with azidation, reduction and addition to get 4β-isothiocyanate-4-deoxypodophyllotoxin (4), which was then reacted with a hydrazide compound to give the thiosemicarbazone derivative. Finally, The target compound was obtained. MTT assay was used to evaluate the inhibitory effect of the target compounds on human prostate cancer cell line DU-145, human gastric cancer cell line SGC-7901, human non-small cell lung cancer cell line 5-fluorouracil, podophyllotoxin and VP- (A549), SH-SY5Y, HepG2, HeLa and 1 normal human fibroblast cells (L929) . Results Nine new compounds were synthesized and their structures were confirmed by IR, 1H-NMR, 13C-NMR and MS. In vitro anti-cancer activity experiments show that the target compounds on normal cells are far less toxic than the positive control, some compounds showed good anti-cancer activity. Conclusion In this series of derivatives, compound 6b shows outstanding biological activity on the cytotoxic activity of the tested cell lines.