新型2-三氟甲基-4-氨基喹啉衍生物的合成及抗肿瘤活性研究

Synthesis and Antitumor Activities of Novel 2-Trifluoromethyl-4-aminoquinoline Derivatives

以4-氟苯胺为起始原料,依次经环合、氯化、偶联、烷基化、还原以及亲核取代反应,设计并合成了10个新型的2-三氟甲基-4-氨基喹啉衍生物(5a~5e、6、7a~7d),其结构经^(1)H NMR、^(13)C NMR、^(19)F NMR及MS(ESI)表征。采用MTT法评价了目标化合物对前列腺癌细胞(PC3、LNCaP)和慢性髓系白血病细胞(K562)的体外抑制活性。结果表明:在5μmol·L^(-1)浓度下,化合物5b、5c及6对PC3细胞的抑制率,以及化合物7a对K562细胞的抑制率均优于阳性对照药紫杉醇,抑制率分别为50.6%、52.1%、54.7%及57.6%。

Ten novel derivatives of 2-trifluoromethyl-4-aminoquinoline(5a~5e,6,7a~7d)were designed and synthesized by cyclization,chlorination,coupling,alkylation,reduction and nucleophilic substitution reactions,using 4-fluoroaniline as starting material.The structures were characterized by ^(1)H NMR,^(13)C NMR,^(19)F NMR and MS(ESI).Their anticancer activities in vitro against prostate cancer cells(PC3,LNCaP)and chronic myelogenous leukemia(K562)were demonstrated by MTT assays.The results showed that at the concentration of 5μmol·L^(-1),the inhibitory rates of compound 5b,5c and 6 on PC3 cells and compound 7a on K562 cells were better than the positive control paclitaxel,which inhibitory rates were 50.6%,52.1%,54.7%and 57.6%,respectively.