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。
Abstract
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.
关键词
喹唑啉 /
三氟甲基 /
化学合成 /
抗增殖活性 /
四甲基偶氮唑盐法
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Key words
quinazoline /
trifluoromethyl /
chemical synthesis /
antiproliferative activity /
MTT assay
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中图分类号：
R914
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脚注
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基金
贵州省高层次创新型人才培养计划课题资助(黔科合平台人才[2016]5678);贵州省自然科学基金项目资助(黔科合基础-ZK[2021]一般070)
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