Design, synthesis and biological evaluation of novel 2,4,6-trisubstituted quinazoline derivatives as potential antitumor agents

• Published in: Medicinal chemistry research Vol. 32; no. 8; pp. 1832 - 1850
• Main Authors: Wang, Hao, Wang, Tianci, Chi, Lingling, Yu, Fuqing, Dai, Honglin, Gao, Chao, Si, Xiaojie, Wang, Zhengjie, Liu, Limin, Zhao, Peirong, Zhu, Yingnan, Liu, Hongmin, Zhang, Qiurong
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2023; Springer Nature B.V
• Subjects: Anticancer properties; Antiproliferatives; Antitumor agents; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cancer; Cell cycle; Cell migration; Inorganic Chemistry; Lead compounds; Medicinal Chemistry; Original Research; Pharmacology/Toxicology; S phase; Tumor cell lines; Synthesis; Quinazoline; Cell cycle analysis; Antitumor; Apoptosis
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-023-03114-x

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 IC 50 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