新型丹皮酚嘧啶类化合物的合成及抗肿瘤活性

以丹皮酚为原料,与1,4-二溴丁烷反应合成中间产物2-(4-溴丁烷氧基)-4-甲氧基苯乙酮(2);2与嘧啶类化合物反应合成了11新型个丹皮酚嘧啶类化合物(4a^4k),其结构经1H NMR,13C NMR,IR和MS(ESI)表征。采用MTT法测定目标化合物对HepG2(人肝癌细胞)、MCF-7(人乳腺癌细胞)、HCT-116(人结肠癌细胞)、A549(人肺癌细胞)和LO2(人正常肝细胞)等5种细胞的抑制活性。结果表明:部分化合物表现出一定的抗肿瘤活性,其中6-(2-氟苯基)-5-氰基-4-羟基-2-丹皮酚丁巯基嘧啶(4c)以及6-甲基-4-羟基-2-丹皮酚丁巯基嘧啶(4i)对HCT-116的IC50值分别为(9.22±1.80)μg/mL、(1.32±0.71)μg/mL,优于阳性对照药顺铂。

Synthesis and Anti-tumor Activities of Novel Paeonol-Pyrimidine Derivatives

The intermediate 1-(2-(4-bromobutoxy)-4-methoxyphenyl)ethan-1-one(2)was obtained by the reaction of paeonol with 1,4-dibromobutane.Then,eleven novel paeonol dihydropyrimidine ketone derivatives were synthesized by the reaction of(2)with a series of pyrimidine compounds.The structures of target compounds were characterized by 1H NMR,13C NMR,IR and MS(ESI).The anti-tumor activities against four human cancer lines(HepG2,MCF-7,HCT-116,A549,LO2)were evaluated in vitro by standard MTT assay.The preliminary bioassay results indicated that some target compounds exhibited good anti-tumor activity in some extent.Especially,2-((4-(2-acetyl-5-methoxyphenoxy)butyl)thio)-6-(2-fluorophenyl)-4-oxo-4,5-dihydropyrimidine-5-carbonitrile(4c)and2-((4-(2-acetyl-5-methoxyphenoxy)butyl)thio)-6-methylpyrimidin-4(5H)-one(4i)showed high activities against HCT-116 with IC50 value of(9.22±1.80)and(1.32±0.71)μg/mL,better than the positive control drug(Cisplatin).