Novel penta-1,4-diene-3-one derivatives containing quinazoline and oxime ether fragments: Design, synthesis and bioactivity.
Novel penta-1,4-diene-3-one derivatives containing quinazoline and oxime ether fragments: Design, synthesis and bioactivity.
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DOI：
10.1016/j.bmc.2021.115999
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发表时间：
2021-01
影响因子：
3.5
通讯作者：
Shijun Su;Meihang Chen;Qin Li;Yihui Wang;Shuai Chen;Nan Sun;C. Xie;Z. Huai;Yinjiu Huang;Wei Xue
中科院分区：
文献类型：
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作者：
Shijun Su;Meihang Chen;Qin Li;Yihui Wang;Shuai Chen;Nan Sun;C. Xie;Z. Huai;Yinjiu Huang;Wei Xue
设计并合成了一系列新型的含喹唑啉和肟醚结构的1，4-戊二烯-3-酮衍生物。采用四甲基偶氮唑盐（MTT）法评价了它们的抗癌活性，结果表明大多数化合物对肝癌SMMC-7721细胞具有极强的抑制作用。其中化合物Q2和Q8的IC 50值分别为0.64和0.63 μM，明显优于吉西他滨（1.40 μM）。进一步的机制研究表明，化合物Q2、Q8、Q13和Q19能有效地抑制SMMC-7721细胞的迁移，并通过抑制DNA复制抑制癌细胞的增殖。Western-blot结果表明，化合物Q2和Q8通过调节肝癌细胞中果糖相关蛋白的表达水平，诱导肝癌细胞发生不可逆的凋亡。这些研究表明，含有喹唑啉和肟醚片段的1，4-二烯-3-戊酮衍生物作为潜在的抗癌药物值得进一步研究。
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, compoundsQ2andQ8displayed the more potent inhibitory activity with IC50values of 0.64 and 0.63 μM, which were better than that of gemcitabine (1.40 μM). Further mechanism studies indicated that compoundsQ2,Q8,Q13andQ19could 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 compoundsQ2andQ8induced 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.