噻唑并[3,2-b][1,2,4]三唑酮衍生物的合成及抗癌活性研究

Synthesis and Preliminary Antitumor Activity Evaluation of Thiazolo [3,2-b][1,2,4] triazolone Derivatives

以3,4,5-三甲氧基苯甲酸为原料,经过Claisen缩合等反应设计合成一系列新的噻唑并[3,2-b][1,2,4]三唑-6-酮稠杂环衍生物并测定其体外抗肿瘤活性。目标化合物经~1HNMR、^(13)CNMR和高分辨质谱等表征后,在He La、HCT116、BEL-7402及L-02细胞中用MTT法测定其抑制细胞增殖的程度,并初步判断化合物的体外抗癌活性。结果表明,与临床常用药顺铂(DDP)相比,多数化合物具有抑制肿瘤细胞增殖活性。其中,5-(4-苄氧基苯亚甲基)-2-(3,4,5-三甲氧基苯基)噻唑并[3,2-b][1,2,4]三唑-6(5H)-酮、5-(4-乙酰氧基苯亚甲基)-2-(3,4,5-三甲氧基苯基)噻唑并[3,2-b][1,2,4]三唑-6(5H)-酮、5-(α-呋喃亚甲基)-2-(3,4,5-三甲氧基苯基)噻唑并[3,2-b][1,2,4]三唑-6(5H)-酮和5-(α-噻吩亚甲基)-2-(3,4,5-三甲氧基苯基)噻唑并[3,2-b][1,2,4]三唑-6(5H)-酮对HCT116等3种癌细胞的抑制率高于正常细胞L-02,且对癌细胞有选择性抑制作用,而对正常细胞无毒性,具有良好的后续研究价值。5-(4-氟苯亚甲基)-2-(3,4,5-三羟苯基)噻唑并[3,2-b][1,2,4]三唑-6(5H)-酮对BEL-7402等细胞的抑制率有大幅度提高,但对L-02正常细胞的毒性更大。

Using 3,4,5-trimethoxybenzoic acid as a starting material to synthesized a series of novel derivatives of thiazolo[3,2-b][1,2,4]triazol-6-one by a series of reaction,such as Claisen condensation,and detected the anti-tumor activities in vitro. The structures were characterized by-1HNMR,-（13）CNMR,high resolution mass spectrometry and so on,and the growth inhibitory activities in vitro were evaluated by MTT assay against HeL a,HCT116,BEL-7402 and L-02. The results showed that compared with the common positive anticancer drug cisplatin,the most of the synthesized compounds were expressed inhibitory activities against the four cells lines. Among them,compound 5-（（ 4-benzyloxy） benzylidene）-2-（ 3,4,5-trimethoxyphenyl） thiazolo[3,2-b][1,2,4]triazol-6（ 5H）-one,4-（（ 6-oxo-2-（ 3,4,5-trimethoxyphenyl） thiazolo[3,2-b][1,2,4]triazol-6（ 5H）-ylidene） methyl） phenyl acetate,5-（ furan-2-ylmethylene）-2-（ 3,4,5-trimethoxyphenyl） thiazolo[3,2-b][1,2,4]triazol-6（ 5H）-one and 5-（ thiophen-2-ylmethylene）-2-（ 3,4,5-trimethoxyphenyl） thiazolo[3,2-b][1,2,4]triazol-6（ 5H）-one showed excellent anti-tumor activities in vitro against the three cancer cell lines such as HCT116 cells with low toxicity to L-02 normal cells,have good subsequent research values in the future. The anti-proliferation activities of 5-（ 4-fluorobenzylidene）-2-（ 3,4,5-trihydroxyphenyl） thiazolo[3,2-b][1,2,4]triazol-6（ 5H）-one were increased greatly against several cell lines,such as BEL-7402 cell,but more toxic to L-02 normal cells.