PUBLICATION
Selective stabilization of multiple promoter G-quadruplex DNA by using 2-phenyl-1H-imidazole-based tanshinone IIA derivatives and their potential suppressing function in the metastatic breast cancer
- Authors
- Zeng, L., Wu, Q., Wang, T., Li, L.P., Zhao, X., Chen, K., Qian, J., Yuan, L., Xu, H., Mei, W.J.
- ID
- ZDB-PUB-210904-10
- Date
- 2021
- Source
- Bioorganic chemistry 106: 104433 (Journal)
- Registered Authors
- Keywords
- DNA damage, G-quadruplex DNA, Intermolecular interaction, Molecular docking, Tanshinone IIA derivatives
- MeSH Terms
-
- Abietanes/chemical synthesis
- Abietanes/metabolism
- Abietanes/therapeutic use*
- Angiogenesis Inhibitors/chemical synthesis
- Angiogenesis Inhibitors/metabolism
- Angiogenesis Inhibitors/therapeutic use
- Animals
- Antineoplastic Agents/chemical synthesis
- Antineoplastic Agents/metabolism
- Antineoplastic Agents/therapeutic use*
- Breast Neoplasms/drug therapy*
- Cell Line, Tumor
- Cell Movement/drug effects
- DNA/drug effects*
- DNA/genetics
- DNA/metabolism
- Drug Screening Assays, Antitumor
- G-Quadruplexes/drug effects*
- Humans
- Imidazoles/chemical synthesis
- Imidazoles/metabolism
- Imidazoles/therapeutic use*
- Molecular Docking Simulation
- Molecular Dynamics Simulation
- Molecular Structure
- Neoplasm Metastasis/prevention & control
- Promoter Regions, Genetic
- S Phase Cell Cycle Checkpoints/drug effects
- Structure-Activity Relationship
- Zebrafish
- PubMed
- 33213893 Full text @ Bioorg. Chem.
Citation
Zeng, L., Wu, Q., Wang, T., Li, L.P., Zhao, X., Chen, K., Qian, J., Yuan, L., Xu, H., Mei, W.J. (2021) Selective stabilization of multiple promoter G-quadruplex DNA by using 2-phenyl-1H-imidazole-based tanshinone IIA derivatives and their potential suppressing function in the metastatic breast cancer. Bioorganic chemistry. 106:104433.
Abstract
The G-quadruplex (G4) DNA, which has been developed as a potential anticancer target in drug screening and design, plays a crucial role in the oncogene transcription and translation. Tanshinone IIA derivatives with a planar heterocycle structure may function as G4 stabilizers. We present an innovative case of imidazole-based tanshinone IIA derivatives (1-8) especially compound 4 that improve the selectivity and the binding affinity with G4 DNA and enhance the target tumor inhibition. Cellular and in vivo experiments indicate that the tanshinone IIA derivative 4 inhibits the growth, metastasis, and angiogenesis of triple-negative breast cancer cells possibly through the stabilization of multiple G4 DNAs (e.g., c-myc, K-ras, and VEGF) to induce DNA damage. Further investigation of the intermolecular interaction and the molecular docking indicates that tanshinone IIA derivatives have better selective binding capability to various G4 DNAs than to double-stranded DNA. These findings provide guidance in modifying the molecular structures of tanshinone IIA derivatives and reveal their potential to function as specific G4 stabilizers.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping