甘草素缩胺硫脲类衍生物的合成及抗癌活性

目的研究甘草素缩胺硫脲类衍生物的合成方法及抗癌活性。方法酸性条件下,甘草素与肼基二硫代甲酸甲酯在乙醇中回流缩合成腙,同时二硫代甲酸甲酯基水解成硫代甲酸基,然后在二环己基碳二亚胺(dicyclohexylcarbodiimide,DCC)催化下与相应的胺反应得到目标化合物3a-3j。采用噻唑蓝(methyl thiazolyl tetrazolium,MTT)法,以五氟尿嘧啶(5-fluorouracil,5-FU)为阳性对照药,评价目标化合物对人白血病细胞(K562)、人前列腺癌细胞(DU-145)、人胃癌细胞(SGC-7901)、人结肠癌细胞(HCT-116)、人乳腺癌细胞(MCF-7)、人肝癌细胞(HepG2)、人宫颈癌细胞(Hela)7个肿瘤细胞株及人肾上皮细胞(293)一个正常细胞株的细胞毒活性。结果合成了10个新化合物,其结构经IR、1 H-NMR1、3 C-NMR和MS确证。体外抗癌活性表明大部分衍生物对K562和DU-145有一定的活性。结论从构效关系看,作者推断在甘草素4-C位接入缩胺硫脲基团可以提高抗癌活性。

Synthesis and anticancer activity of liquiritigenin thiosemicarbazone derivatives

Objective To study the synthesis and antitumor activity of liquiritigenin thiosemicarbazone derivatives. Methods Liquiritigenin and methyl hydrazine carbodithioate were refluxed in ethanol in the presence of concentrated hydrochloric acid to give hydrazones, and its alkyldithioate was hydrolyzed to thionocarboxylic acid in the meantime. Afterwards, the hydrazones were treated with various amines and refluxed in ethanol in the presence of DCC to give target compounds 3a-3j. Taking fluorouracil as reference, their antitumor activities were evaluated by MTT method on K562, DU-145, SGC-7901, HCT-116, Hela, HepG2, MCF-7 and 293. Results Ten novel compounds were synthesized, and their structures were characterized by IR, ¹H-NMR, ¹³C-NMR and MS. The results of primary tests indicated that most of the prepared compounds displayed selective cytotoxicity toward K562 and DU-145 cells. Conclusions From the structure-activity relationships it may be concluded that the introduction of a thiosemicarbazone functional group at the 4-position in the skeleton of liquiritigenin is associated with an increase in cytotoxicity.