摘要/Abstract

为了寻找高效低毒的抗肿瘤药物, 设计并合成了一系列新型的含三氟甲基基团的2,4,6-三取代喹唑啉喹唑啉类衍生物, 并采用噻唑蓝(MTT)比色法测定目标化合物对人前列腺癌细胞系(PC-3)、人乳腺癌细胞系(MCF-7)、人食管癌细胞系(Eca-109)、人胃癌细胞系(MGC-803)、人未分化胃癌细胞系(HGC-27)、人非小细胞肺癌细胞系(A549)和人非小细胞肺癌细胞系(H1975)的抗肿瘤活性. 结果显示部分化合物表现出中度至强效的抗肿瘤活性, 其中N-(3-溴苯基)-6-甲氧基-2-((4-(三氟甲基)苄基)硫代)喹唑啉-4-胺(16l)对PC-3细胞具有最好的抗肿瘤活性, IC₅₀值为(2.22±0.15) μmol/L, 抗肿瘤活性明显优于阳性对照品吉非替尼. 此外, 化合物16l对PC-3细胞以浓度依赖与时间依赖的方式诱导其凋亡.
关键词: 三氟甲基, 喹唑啉, 合成, 抗肿瘤活性
In order to find efficient and low toxicity antitumor drugs, a series of novel 2,4,6-trisubstituted quinazoline derivatives containing trifluoromethyl were synthesized and evaluated for their antitumor activities against human cancer cell lines (PC-3, MCF-7, Eca-109, MGC-803, HGC-27, A549, H1975) by using methyl thiazolyl tetrazolium (MTT) assay. Most of compounds exerted moderate to excellent antitumor activity against seven human cancer cells. Among them, N-(3-bromophenyl)-6-methoxy-2-((4-(trifluoromethyl)benzyl)thio)quinazolin-4-amine (16l) showed the best antitumor activity against PC-3 cancer cell line, with the IC₅₀ values of (2.22±0.15) μmol/L, which was better than the positive control of gefitinib. At the same time, and compound 16l could dose-dependently and time-dependently induce PC-3 cells apoptosis.
Key words: trifluoromethyl, quinazoline, synthesis, antitumor activity


PDF全文下载地址:

点我下载PDF