Su Shijun, Chen Mei, Li Qin, Wang Yihui, Chen Shuai, Sun Nan, Xie Chengwei, Huai Ziyou, Huang Yinjiu, Xue Wei
State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang, Guizhou 550025, China.
School of Life Science, Bengbu Medical College, Anhui, Bengbu 233030, China.
Bioorg Med Chem. 2021 Feb 15;32:115999. doi: 10.1016/j.bmc.2021.115999. Epub 2021 Jan 6.
A series of novel penta-1,4-diene-3-one derivatives containing quinazoline and oxime ether moieties were designed and synthesized. Their anticancer activities were evaluated by MTT assay, the results showed that most compounds exhibited extremely inhibitory effects against hepatoma SMMC-7721 cells. In particular, compounds Q2 and Q8 displayed the more potent inhibitory activity with IC values of 0.64 and 0.63 μM, which were better than that of gemcitabine (1.40 μM). Further mechanism studies indicated that compounds Q2, Q8, Q13 and Q19 could control the migration of SMMC-7721 cells effectively, and inhibit the proliferation of cancer cells by inhibiting the DNA replication. Western-blot results showed that compounds Q2 and Q8 induced irreversible apoptosis of SMMC-7721 cells by regulating the expression level of apoptose-related proteins. Those studies demonstrated that the penta-1,4-diene-3-one derivatives containing quinazoline and oxime ether fragments merited further research as potential anticancer agents.
设计并合成了一系列含喹唑啉和肟醚基团的新型戊-1,4-二烯-3-酮衍生物。通过MTT法评估了它们的抗癌活性，结果表明大多数化合物对肝癌SMMC-7721细胞表现出极强的抑制作用。特别是，化合物Q2和Q8表现出更强的抑制活性，IC值分别为0.64和0.63 μM，优于吉西他滨（1.40 μM）。进一步的机制研究表明，化合物Q2、Q8、Q13和Q19可以有效控制SMMC-7721细胞的迁移，并通过抑制DNA复制来抑制癌细胞的增殖。蛋白质免疫印迹结果表明，化合物Q2和Q8通过调节凋亡相关蛋白的表达水平诱导SMMC-7721细胞发生不可逆凋亡。这些研究表明，含喹唑啉和肟醚片段的戊-1,4-二烯-3-酮衍生物作为潜在的抗癌药物值得进一步研究。
