PUBLICATION
Synthesis, docking studies and antitumor activity of phenanthroimidazole derivatives as promising c-myc G-quadruplex DNA stabilizers
- Authors
- Wu, Q., Song, Y., Liu, R., Wang, R., Mei, W., Chen, W., Yang, H., Wang, X.
- ID
- ZDB-PUB-200802-13
- Date
- 2020
- Source
- Bioorganic chemistry 102: 104074 (Journal)
- Registered Authors
- Keywords
- Apoptosis, C-myc G-quadruplex DNA, DNA damage, Mitochondrial dysfunction, Nasopharyngeal carcinoma, Phenanthroimidazole derivatives
- MeSH Terms
-
- Animals
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/therapeutic use*
- DNA/chemistry*
- G-Quadruplexes
- Humans
- Imidazoles/chemical synthesis*
- Imidazoles/pharmacology
- Imidazoles/therapeutic use*
- Molecular Docking Simulation
- Nasopharyngeal Carcinoma/drug therapy*
- Nasopharyngeal Carcinoma/pathology
- Zebrafish
- PubMed
- 32738566 Full text @ Bioorg. Chem.
Citation
Wu, Q., Song, Y., Liu, R., Wang, R., Mei, W., Chen, W., Yang, H., Wang, X. (2020) Synthesis, docking studies and antitumor activity of phenanthroimidazole derivatives as promising c-myc G-quadruplex DNA stabilizers. Bioorganic chemistry. 102:104074.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping