罗丹宁衍生物的合成及抗肿瘤活性

Synthesis and anti-tumor activity of rhodanine derivatives

在罗丹宁衍生物WL-276的基础上设计并合成一系列新的罗丹宁衍生物,并对这些化合物的抗肿瘤活性进行测定。以氨基酸为原料,经环合和缩合反应,合成了化合物Ⅱ1-4,然后分别与硫化氢供体ADT-OH偶联得到化合物Ⅲ1-4,共合成了8个目标化合物,其中4个未见报道,其结构均经1H NMR、IR和HR-MS确证。然后用MTT法筛选其抗肿瘤活性。初步研究表明,化合物Ⅱ1,3,4和Ⅲ1-4对HepG2肿瘤细胞和DU145肿瘤细胞的增殖均具有较强的抑制作用,且化合物Ⅲ的活性比Ⅱ强;化合物Ⅲ2,4对HepG2细胞和化合物Ⅲ1,2,4对DU145细胞的抗增殖活性均高于阳性对照5-氟尿嘧啶。

Based on the study of rhodanine derivative WL-276,some novel compounds were synthesized,and their anti-tumor effects were screened by MTT method.Compounds II1-4 were obtained by cyclization and condensation from the certain amino acids,and then coupled respectively with hydrogen sulfide donor ADT-OH to afford compounds III1-4,whose structures were confirmed by 1H NMR,IR and HR-MS.Furthermore,preliminary pharmacological results suggested that compounds II1,3,4,III1-4 had strong inhibitory effects on the proliferation of HepG2 and DU145 tumor cells.Particularly,the anti-proliferation activity of compounds III2,4 on HepG2 and compounds III1,2,4 on DU145 tumor cells was stronger than that of the positive control,5-fluorouracil.