新型含芳基哌嗪的苯并噻唑衍生物的设计、合成及活性研究

Design, synthesis and activities of novel benzothiazole derivatives containing arylpiperazine

应用生物电子等排原理,设计并合成了两类共24个含芳基哌嗪的苯并噻唑衍生物。采用MTT法评价了化合物对4种癌细胞和2种正常细胞的抗增殖作用。结果表明,大部分化合物对于癌细胞的增殖都有一定程度的抑制作用,其中化合物II2、II3、II6和II7对HepG2和HeLa229细胞具有较强的抗增殖作用,其IC50值分别为1.6～4.5μmol.L 1和2.5～5.3μmol.L 1;苯环对位引入氰基的化合物(Ι4、Ι8、Ι12、II4、II8、II12)对AsPC-1细胞具有较好的抗增殖作用,IC50值为5.2～11.3μmol.L 1,在此基础上初步探讨了此类化合物的构效关系。

Twenty-four novel benzothiazole derivatives containing arylpiperazine were designed and synthesized by bioisosterism principle. Anti-proliferative effect of these synthesized compounds against four cancer cell and two normal cell lines were evaluated in vitro by the standard MTT assay. Pharmacological test showed that most of the compounds exhibited potent antitumor activity. Some of the compounds （Ⅱ2,Ⅱ3,Ⅱ6 ,Ⅱ7） showed strong anti-proliferation activities against HepG2 and HeLa229 cell lines with the IC 50 values of 1.6-4.5 μmol·L^-1 and 2.5-5.3 μmol·L^-1, respectively, and compounds having eyan in p-substituted benzene ring （Ⅰ4,Ⅰ8,Ⅰ2,Ⅱ4,Ⅱ8,Ⅱ12） were found to have better antitumor activities against AsPC-1 cell lines with the IC50 values of 5.2-11.3 μmol·L^-1, The structure-activity relationship of benzothiazole derivatives containing arylpiperazine was also discussed preliminarily.