紫檀芪查尔酮衍生物的合成及抗肿瘤活性研究

Synthesis and Antitumor Activity of Pterostilbene Chalcone Derivatives

以紫檀芪为先导化合物,将其酚羟基甲氧基化,引入醛基,并与丹皮酚乙酸通过羟醛缩合反应合成紫檀芪查尔酮苯氧乙酸,再与不同的有机胺反应得到10个目标化合物。所有目标化合物经核磁共振氢谱、质谱进行结构确证。采用MTT法初步评价目标化合物对人肝癌细胞HepG2、人非小细胞肺癌细胞A549、人骨肉瘤细胞U-2OS的体外抗肿瘤活性,同时采用ELISA法检测目标化合物对组蛋白去乙酰化酶(HDAC)的抑制能力。结果表明大部分目标化合物抗肿瘤活性高于紫檀芪,其中化合物(E)-3-(2,4-二甲氧基-6-((E)-4-甲氧基苯乙烯基)苯基)-1-(4-甲氧基-2-(2-吗啉基-2-氧代乙氧基)苯基)丙-2-烯-1-酮(5a)对U-2OS细胞的IC 50值达到了(6.10±1.11)μmol/L。同时,该化合物在25μmol/L时,对HDAC1和HDAC2的抑制率可达40%左右。

Using pterostilbene as the lead compound,its phenolic hydroxyl group was methoxylated,and the aldehyde group was introduced to synthesise zitanica astragali chalcone phenoxyacetic acid via hydroxyaldehyde condensation with salvianolic acid,and synthesize 10 target compounds by reacting with different organic amines.The target compounds were confirmed by NMR hydrogen spectroscopy and mass spectrometry.MTT method was used to initially evaluate the in vitro antitumour activities of the target compounds against human hepatocellular carcinoma cells HepG2,human non-small cell lung cancer cells A549,and human osteosarcoma cells U-2OS,while the inhibitory ability of the target products against histone deacetylase(HDAC)was monitored by ELISA.The results showed that most of the target compounds had higher antitumour activities than pterostilbene,and the compound(E)-3-(2,4-dimethoxy-6-((E)-4-methoxystyryl)phenyl)-1-(4-methoxy-2-(2-morpholino-2-oxoethoxy)phenyl)prop-2-en-1-one(5a)reached an IC 50 value of(6.10±1.11)μmol/L against U-2OS cells.Meanwhile,the compound inhibited HDAC1 and HDAC2 up to about 40%at 25μmol/L.