目的 对基于由冬虫夏草提取物多球壳菌素ISP-1结构改造而得到的药物芬戈莫德进行结构修饰,并初步考察其类似物的抗肿瘤活性。方法 以不同的取代苯为原料,按照本课题组开发的芬戈莫德合成路线,经过傅克酰基化、亚硝基S_N2取代反应、羰基还原、双亨利反应和硝基还原反应制得目标化合物。通过MTT方法,检测化合物对3种人类肿瘤细胞Siha、PC-3和MKN-45的抗肿瘤活性。结果 制得芬戈莫德(1)及其18个类似物(2～19),化合物10、11、12具有与芬戈莫德相当的抗肿瘤活性。结论 化合物2～10及12～19为未见文献报道的新化合物,为基于1-磷酸鞘氨醇(S1P)受体拮抗作用的抗肿瘤药物的发现提供依据。

Objective To modify the structure of fingolimod which was derived from the extract of medicinal plant Cordyceps ISP-1 and evaluate the antitumor activity of the derivatives. Methods According to the synthesis way developed before, target compounds were synthesized by using suitable substitued benzenes, through chemical reactions such as Friedel-Crafts reaction, Nitros-substitution reaction, Carbonyl reduction, Henry reaction, and Nitro-reduction. The cytotoxicities to three cell lines, Siha, PC-3, and MKN-45, were evaluated through MTT method. Results Fingolinod and 18 fingolimod analogues were synthesized, and compounds 10—12 had the equal antitumor activities like fingolimod. Conclusion The compounds 2—10, 12—19 are new compounds not reported before. This study provides the foundation for finding antitumor compounds with S1PRs inhibiting effect.

烟台大学研究生科技创新基金资助(01082)