新型2-(4-喹啉/喹唑啉)硫代苯并噻唑类化合物的合成与抗肿瘤活性的评价  

Synthesis and preliminary evaluation of novel 2-(quinolin-4-ylthio) benzothiazole derivatives as potential anticancer agents

作　　者：李潇[1] 赵立峰[1] 刘志昊[1] 余洛汀[1] 

机构地区：[1]四川大学华西医院生物治疗国家重点实验室,四川成都610041

出　　处：《华西药学杂志》2013年第6期560-562,共3页West China Journal of Pharmaceutical Sciences

摘　　要：目的设计并制备了11个新型2-(4-喹啉/喹唑)啉硫代-6-氨基苯并噻唑类化合物,并探讨其抗肿瘤活性。方法依据拼合原理,将2-巯基-6-氨基苯并噻唑和4-氯-6,7-二甲氧基喹唑啉(或喹啉)两个片段结合,形成关键结构并据此合成系列衍生物,用MTT法进行体外抗肿瘤活性评价和构效关系研究。结果与结论合成的11个新化合物Ia^Ik未见文献报道;其中化合物Ic对黑色素瘤细胞株A2058的IC50为21.2μmol·L-1(Sorafenib 23.5μmol·L-1);化合物Ib、Ic对黑色素瘤细胞株A875的IC50分别为25.4、27.0μmol·L-1(Sorafenib 28.5μmol·L-1),显示的活性均优于阳性对照药物,但对测试的其他肿瘤细胞株均未显示活性。OBJECTIVE To synthesize eleven 2 - （6,7 - dimethoxyquinolin - 4 - ykhio） benzol d] thiazol - 6 - amine derivatives, and evaluate their anticancer activities. METHODS According to combination principles, the target compounds were synthesized from the reactions of 6 - aminobenzo [ d ] thiazole - 2 - thiol and 4 - chloro - 6,7 - dimethoxyquinoline （ quinazoline ） , followed by different acyl chloride. The preliminary anticancer activity was tested by the MTT assay. RESULTS and CONCLUSION Eleven novel target compounds I a - I k were synthesized. Among these compounds, ICso value of compound Ic was 21.2 μmol·L-1 （Sorafenib was 23.5 μmol·L-1 ） against A2058; ICs~ values of compound Ib, Ic were 25.4,27.0 μmol·L-1 （Sorafenib was 28.5 μmol·L-1 ） against A875, respectively. The evaluation in vitro showed they had higher anti - tumor activity against melanoma cell than Sorafenib as positive control. However,they exhibited no activity against the other cell lines which have been tested.

关 键 词：2-巯基苯并噻唑 喹啉 结构拼合 抗肿瘤活性 黑色素瘤 

分 类 号：R914[医药卫生—药物化学]