论文部分内容阅读
目的:为寻找新型一氧化氮(NO)供体型抗肿瘤候选药物,设计合成了一系列新型呋咱类1-位氧代冬凌草甲素衍生物。方法:首先合成不同呋咱类NO供体中间体(9a-i),再将它们与1-位氧代冬凌草甲素(2)的14-位羟基进行缩合,得到一系列NO供体型呋咱类1-位氧代冬凌草甲素衍生物;用Griess实验测试硝酸盐/亚硝酸盐的含量,从而间接测试了NO释放量;同时采用MTT法测定了目标化合物对4种人肿瘤细胞株增殖的抑制活性。结果:所有呋咱类NO供体衍生物在体外60min时间点上都能释放大于19 μmol·L-1的NO。活性最好的目标化合物10h对Bel-7402细胞的增殖抑制活性IC50值达到0.74μmol·L-1, 优于阳性对照药紫杉醇;获得了初步构效关系信息。结论:利用NO供体和活性天然产物形成孪药分子有望成为发现新型抗肿瘤药物的途径之一。
OBJECTIVE: To search a new type of antitumor drug candidate for nitric oxide (NO), a series of novel furazan 1-oxo-oridonin derivatives were designed and synthesized. Methods: First, different donor furazan intermediates (9a-i) were synthesized and then condensed with the hydroxyl group at the 14-position of 1-oxo-oridin (2) to obtain a series of NO donors Furazan 1-position oxo-oridin derivatives; Nitrite / nitrite content was tested by Griess test to indirectly test NO release; meanwhile MTT method was used to determine the effect of the target compound on four kinds of human tumors Cell proliferation inhibitory activity. Results: All furazan NO donor derivatives released more than 19 μmol·L-1 NO at 60min in vitro. The IC50 value of target compound 10h on Bel-7402 cells reached 0.74μmol·L-1 at 10h, which was superior to the positive control paclitaxel. The preliminary structure-activity relationship information was obtained. Conclusion: It is expected that the use of NO donors and active natural products to form twinning molecules will be one of the ways to find new antitumor drugs.