In this study, a series of novel 2,4,6-trisubstituted quinazoline derivatives were designed, synthesized and biologically evaluated their antiproliferative activity against four human cancer cell lines (Eca-109, A549, PC-3 and MGC-803). The most of designed compounds showed considerable antiproliferative activity against the tested four cancer cell lines, while compound 28g displayed the best antiproliferative activity with the IC₅₀ values of 1.95 μM and 2.46 μM against MGC-803 cells and Eca-109 cells, respectively. Further mechanism studies indicated that 28g significantly inhibited the cell migration and colony formation of MGC-803 cells. Besides, 28g also dose-dependently induced cellular apoptosis and cell cycle arrest at S phase in MGC-803 cells. Overall, all these studies suggested that 28g has the potential to act as a valuable lead compound for the development of antitumor agents.

Graphical Abstract

中文翻译：

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新型2,4,6-三取代喹唑啉衍生物作为潜在抗肿瘤药物的设计、合成和生物学评价

在这项研究中，设计、合成了一系列新型2,4,6-三取代喹唑啉衍生物，并从生物学角度评估了它们对四种人类癌细胞系（Eca-109、A549、PC-3和MGC-803）的抗增殖活性。大多数设计的化合物对测试的四种癌细胞系表现出相当大的抗增殖活性，而化合物28g对MGC-803细胞和Eca-109细胞表现出最好的抗增殖活性，其IC ₅₀值分别为1.95 μM和2.46 μM。进一步的机制研究表明，28g显着抑制MGC-803细胞的细胞迁移和集落形成。另外，28克还在 MGC-803 细胞中剂量依赖性地诱导细胞凋亡和细胞周期停滞在 S 期。总体而言，所有这些研究表明28g有潜力作为抗肿瘤药物开发的有价值的先导化合物。

图形概要