司他夫定衍生物的合成及抗肿瘤活性评价

目的设计合成一系列司他夫定类衍生物,并评价其抗肿瘤活性。方法以司他夫定为原料,经磺酸酯化后与叠氮化钠反应生成5'-叠氮基司他夫定,再通过Huisgen 1,3-偶极环加成反应得到目标化合物。采用MTT法分别以人肝癌细胞(BEL-7402)、人胃癌细胞(BGC-823)、肺癌细胞(A549)为测试细胞株对目标化合物进行体外抗肿瘤活性评价。结果与结论合成了14个5'-脱氧司他夫定衍生物,目标化合物的结构经核磁共振氢谱和碳谱确证。其中化合物4k对人肝癌细胞(BEL-7402)、人胃癌细胞(BGC-823)、肺癌细胞(A549)具有中等的抑制作用。

Synthesis and antitumor activity of stavudine derivatives

Many nucleoside analogs are rationally designed as anticancer drugs used clinically for both solid tumors and hematological malignancies. Despite the availability of several nucleoside analogues in the clinic, the development of newer agents with improved properties is still demanded to overcome issues of resis- tance, poor oral bioavailability, long-term toxicity. The introduction of a triazole ring into nucleosides to im- prove bioactivity in antitumor and antivirus agents has become widespread in drug design practices. Starting from stavudine via mesylation, azidation and Cu-catalyzed azide-alkyne cycloaddition,totally 16 target com- pounds were synthesized and all of them were not reported yet, and all of them were confirmed by 1H-NMR and 13 C-NMR. Among them, compound 4k showed moderate activity against tumor cell lines, BEL7402 （60. 49 μmol· L -1 ）, BGC823 （30. 00 ixmol- L - 1 ） and A549 （40. 85 p, mol- L - 1 ）. The result might suggest that the conjugation effects of the triazole ring with the aromatic system may be essential for bioactivity.