Abstract：
A novel series of trifluoromethyl-containing quinazoline derivatives with a variety of functional groups was designed, synthesized, and tested for their antitumor activity by following a pharmacophore hybridization strategy. Most of the 20 compounds displayed moderate to excellent antiproliferative activity against five different cell lines (PC3, LNCaP, K562, HeLa, and A549). After three rounds of screening and structural optimization, compound 10 b was identified as the most potent one, with IC50 values of 3.02, 3.45, and 3.98 μM against PC3, LNCaP, and K562 cells, respectively, which were comparable to the effect of the positive control gefitinib. To further explore the mechanism of action of 10 b against cancer, experiments focusing on apoptosis induction, cell cycle arrest, and cell migration assay were conducted. The results showed that 10 b was able to induce apoptosis and prevent tumor cell migration, but had no effect on the cell cycle of tumor cells.
摘要：
设计了一系列具有多种官能团的新型含三氟甲基喹唑啉衍生物，合成，并按照药效团杂交策略测试其抗肿瘤活性。20种化合物中的大多数对五种不同的细胞系（PC3，LNCaP，K562,HeLa,A549）。经过三轮筛选和结构优化,化合物10b被确定为最有效的化合物，对PC3、LNCaP的IC50值为3.02、3.45和3.98μM，和K562细胞，分别,与吉非替尼阳性对照的效果相当。为了进一步探讨10b的抗癌作用机制，专注于凋亡诱导的实验，细胞周期停滞,并进行细胞迁移试验。结果表明，10b能够诱导细胞凋亡，阻止肿瘤细胞迁移，但对肿瘤细胞的细胞周期没有影响。
