4-氨基-2-三氟甲基喹唑啉衍生物的合成及其体外抗肿瘤活性研究

目的 基于喹唑啉为母核设计发现新型抗肿瘤活性化合物。方法 以邻氨基苯甲酰胺和三氟乙酸酐为起始原料采用缩合、环化、氯代和偶联反应等合成了一系列4-氨基-2-三氟甲基喹唑啉衍生物(5a~5u)。采用四甲基偶氮唑盐(MTT)法评价所得目标化合物对人肺癌细胞A549、人宫颈癌细胞Hela、人白血病细胞K562、人前列腺癌细胞PC-3、人前列腺癌细胞LNCaP这5种肿瘤细胞的体外增殖抑制活性。结果 化合物5c在5 μmol·L^-1时对PC-3肿瘤细胞的抑制率为49.3%,化合物6a对LNCaP和K562、以及6b对PC-3的抑制率超过了50.0%。结论 本实验设计合成的4-氨基-2-三氟甲基喹唑啉类化合物多数具有一定的抗肿瘤活性,特别是4-氨基的N-甲基化产物6a、6b的体外抗肿瘤活性较原型化合物(5n与5u)显著增强,为该类化合物的进一步研究提供参考。

Synthesis and Antitumor Activities of 4-Amino-2-Trifluoromethyl Quinazoline Derivatives

OBJECTIVE To search for and synthesize series of novel anti-tumor quinazoline derivatives.METHODS A series of 4-amino-2-trifluoromethyl quinazoline derivatives were synthesized by condensation, cyclization, chlorination and coupling reaction starting from 2-aminobenzamide.Their anti-proliferative activity against A549, Hela, K562, PC-3 and LNCaPcell lines were evaluated by MTT assay.RESULTS Compound 5c exhibited certain inhibitory activity against PC-3 cell line with inhibitory values of 49.3% at 5 μmol·L^-1. The inhibition rate of 6a against LNCaP and K562 was higher than 50.0%as well as compound 6b against PC-3.CONCLUSION Some of the target compounds show certain inhibitory activities against LNCaP, PC-3 and Hela tumor cell lines. In particular, the anti-tumor activities of N-methylated products 6a and 6b are significantly higher than those of the prototype compounds(5n and 5u), which provides a basis for the further study of these compounds.