Synthesis, docking studies and antitumor activity of phenanthroimidazole derivatives as promising c-myc G-quadruplex DNA stabilizers

被引:19
作者
Wu, Qiong [1 ,3 ]
Song, Yue [1 ]
Liu, Ruotong [2 ,3 ]
Wang, Rui [1 ]
Mei, Wenjie [2 ,3 ,4 ]
Chen, Weiming [2 ,3 ]
Yang, Huanglan [2 ,3 ]
Wang, Xicheng [1 ]
机构
[1] Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China
[2] Guangdong Pharmaceut Univ, Sch Pharm, Guangzhou 510006, Peoples R China
[3] Guangdong Prov Engn Technol Ctr Mol Probe & Biome, Guangzhou 510006, Peoples R China
[4] Guangdong Pharmaceut Univ, Guangzhou Key Lab Construct & Applicat New Drug S, Guangzhou 510006, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
Phenanthroimidazole derivatives; Nasopharyngeal carcinoma; Mitochondrial dysfunction; DNA damage; Apoptosis; C-myc G-quadruplex DNA; MICROWAVE-ASSISTED SYNTHESIS; OXIDATIVE STRESS; CANCER-CELLS; DAMAGE; MITOCHONDRIA; ANTICANCER; EXPRESSION; COMPLEXES; ZEBRAFISH; ASSAY;
D O I
10.1016/j.bioorg.2020.104074
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Phenanthroimidazole derivatives containing phenanthroline and imidazole heterocyclic aromatic rings are effective agents to inhibit tumor cell growth. Herein, halogen element-modified imidazo[4,5f][1,10]phenanthroline derivatives 1-6 (1, 4-fluorophenyl; 2, 4-chlorophenyl; 3, 4-bromobenyl; 4, 2,3-dichlorophenyl; 5, 3,4-dichlorophenyl; and 6, 2,4-dichlorophenyl) were synthesized, and their antitumor activities were investigated. All of the compounds, especially 4, exhibited an excellent inhibitory effect against nasopharyngeal carcinoma CNE-1 cells. This effect was better than that of doxorubicin. Compound 4 also markedly blocked the proliferation of the CNE-1 cells in a zebrafish xenograft model. The antitumor mechanisms might be attributed to apoptosis induction, which triggered ROS-mediated DNA damage and generated mitochondrial dysfunction by stabilizing c-myc G-quadruplex DNA structure. Results indicated that phenanthroimidazole derivatives could act as promising anticancer agents.
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页数:14
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