氮芥型槐定碱衍生物的合成及抗肿瘤活性

Synthesis and Anti-cancer Activivity of Nitrogen Mustard Sophoridine Derivatives

为了发现更好的抗肿瘤药物,以均具有抗肿瘤活性的槐定碱和氮芥互为药效基团,并以槐定碱为原料,合成了6种未见文献报道的标题化合物,所得产物经过1HNMR、MS和元素分析确证。采用MTT法测试所合成化合物的体外抗肿瘤活性,结果表明,所有目标化合物的抗肿瘤活性均强于母体槐定碱,其中12-苄基槐定酸17-{4-[N,N-二(2-氯乙基)]}苯甲酰胺对肝癌细胞HepG2的抑制活性与商品药物美法仑相当。

In order to find more effective anticancer drugs, both sophoridine and nitrogen mustard have anti-tumor activi- ty, and using them as pharmacophore. Six nitrogen mustard so- phoridine target compounds were synthesized utilizing sophori- dine as starting material. The structures of target compounds were confirmed by elemental analysis, I HNMR and MS. All target compounds exhibited expeetedly much more stronger anti human hepatocellular carcinoma cells （HepG2 cells） ac- tivity than that of parent compound sophoridine in viva. Fur- thermore,the cyt0toxic activities of 12-acid benzyl sophoridine 17- { 4- [ N, N-bis （ 2-chloroethyl ） ] t benzamide was similar to the commercial drug Melphalan. The concept of designing ni- trogen mustard sophoridine derivatives that possess potent an- ticaneer activity warrants further investigation.