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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SN2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 based on the structural modification of Cordyceps sinensis ISP-1, and to study the antitumor activity of its analogs. Methods Different substituted benzenes were used as raw materials to prepare target compounds according to the fingolimod synthesis route developed by our group via Friedel-Crafts acylation, nitroso-SN2 substitution, carbonyl reduction, double Henry reaction and nitro reduction . The anti-tumor activity of the compounds on three human tumor cells Siha, PC-3 and MKN-45 was tested by MTT assay. Results Fingolimod (1) and its 18 analogues (2-19) were prepared and compounds 10, 11, 12 had antitumor activity comparable to that of fingolimod. Conclusion Compounds 2 ~ 10 and 12 ~ 19 are new compounds which have not been reported in the literature, which provide the basis for the discovery of antitumor drugs based on the antagonism of sphingosine-1-phosphate receptor.