共 54 条
Synthesis, docking studies and antitumor activity of phenanthroimidazole derivatives as promising c-myc G-quadruplex DNA stabilizers
被引:19
作者:

Wu, Qiong
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Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China
Guangdong Prov Engn Technol Ctr Mol Probe & Biome, Guangzhou 510006, Peoples R China Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China

Song, Yue
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Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China

Liu, Ruotong
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机构:
Guangdong Pharmaceut Univ, Sch Pharm, Guangzhou 510006, Peoples R China
Guangdong Prov Engn Technol Ctr Mol Probe & Biome, Guangzhou 510006, Peoples R China Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China

Wang, Rui
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Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China

Mei, Wenjie
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Guangdong Pharmaceut Univ, Sch Pharm, Guangzhou 510006, Peoples R China
Guangdong Prov Engn Technol Ctr Mol Probe & Biome, Guangzhou 510006, Peoples R China
Guangdong Pharmaceut Univ, Guangzhou Key Lab Construct & Applicat New Drug S, Guangzhou 510006, Peoples R China Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China

Chen, Weiming
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机构:
Guangdong Pharmaceut Univ, Sch Pharm, Guangzhou 510006, Peoples R China
Guangdong Prov Engn Technol Ctr Mol Probe & Biome, Guangzhou 510006, Peoples R China Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China

Yang, Huanglan
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h-index: 0
机构:
Guangdong Pharmaceut Univ, Sch Pharm, Guangzhou 510006, Peoples R China
Guangdong Prov Engn Technol Ctr Mol Probe & Biome, Guangzhou 510006, Peoples R China Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China

Wang, Xicheng
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h-index: 0
机构:
Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China Guangdong Pharmaceut Univ, Affiliat Hosp 1, Guangzhou 510062, Peoples R China
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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