L-鼠李糖氮杂核苷衍生物的设计、合成及抗癌活性研究

Design Synthesis and Antitumor Activities of L-rhamnopyranosyl-5-azacytidine

L-鼠李糖及L-鼠李糖结构的化合物具有较好的抗肿瘤活性及选择性,为了降低DNA甲基转移酶抑制剂氮杂胞苷的毒副作用,以氮杂胞苷为先导化合物设计、合成了7个L-鼠李糖氮杂核苷衍生物,其结构经核磁和元素分析确证.对目标化合物对两种细胞系进行了体外增值活性研究,4-氨基-1,3,5-三嗪-1-硫代-α-L-鼠李糖核苷(5D)对MKN-45细胞具有中等强度的抗癌活性,可作为先导化合物进一步研究.

The compounds bearing L-rhamnopyranoside moieties and L-rhamnose have better antitumor activity and selectivity.In order to decrease the cytotoxic effects and increase the activities of DNA methyltransferase inhibition,the severα-L-rhamnopyranosides using 5-azacytidine as lead compound have been designed and synthesized.The target compounds were confirmed by 1 H-NMR and MS.The cytotoxic activities were evaluated against MKN-45 and Hela cell lines.The compound 4-amino-1,3,5-triazin-2-yl-1-thio-α-L-rhamnopyranoside(5 D)showed a moderate antitumor ability against MKN-45 cell line and maybe become a lead compound for further development.