PUBLICATION
Phenanthroimidazole derivatives act as potentinducer of autophagy by activating DNA damage pathway
- Authors
- Zhang, H., Song, Y., Li, L., Zhang, S.Y., Wu, Q., Mei, W.J., Liu, H.M., Wang, X.C.
- ID
- ZDB-PUB-190428-4
- Date
- 2019
- Source
- Bioorganic chemistry 88: 102940 (Journal)
- Registered Authors
- Keywords
- Apoptosis Inducer, Autophagy, DNA damage, Hepatocellular carcinoma, Phenanthroline derivative, Zebrafish
- MeSH Terms
-
- Animals
- Antineoplastic Agents/chemical synthesis
- Antineoplastic Agents/chemistry
- Antineoplastic Agents/pharmacology*
- Autophagy/drug effects*
- Cell Cycle/drug effects
- Cell Proliferation/drug effects
- Cell Survival/drug effects
- DNA Damage
- DNA, Neoplasm/drug effects*
- Drug Screening Assays, Antitumor
- Humans
- Imidazoles/chemical synthesis
- Imidazoles/chemistry
- Imidazoles/pharmacology*
- Liver Neoplasms/drug therapy*
- Liver Neoplasms/pathology
- Liver Neoplasms, Experimental/drug therapy
- Liver Neoplasms, Experimental/pathology
- Phenanthrolines/chemical synthesis
- Phenanthrolines/chemistry
- Phenanthrolines/pharmacology*
- Tumor Cells, Cultured
- Zebrafish
- PubMed
- 31028991 Full text @ Bioorg. Chem.
Citation
Zhang, H., Song, Y., Li, L., Zhang, S.Y., Wu, Q., Mei, W.J., Liu, H.M., Wang, X.C. (2019) Phenanthroimidazole derivatives act as potentinducer of autophagy by activating DNA damage pathway. Bioorganic chemistry. 88:102940.
Abstract
A series of imidazo[4,5f][1,10]phenanthroline derivatives (1-6) have been synthesized in this study, and their inhibitory activity was evaluated by MTT assay. Results showed that all of these compounds demonstrate a promising inhibitory activity against a panel of human cancer cell lines. The 6, the most effective compound with IC50 of approximately 2.3 ± 0.1 µM, was against the growth and could induce autophagy of HepG2 cells. This condition was confirmed by abundant autophagic vacuoles appearing in cells and evident ultrastructural changes observed under transmission electron microscopy. The autophage induced by 6 has also been demonstrated by up-regulating LC3-II and Beclin1. The apoptosis and G2/M phase cell cycle arrest through DSB damage have also been confirmed after the HepG2 cells were treated by 6. These multiple effects, especially induction apoptosis and autophagy, indicate the potential of 6 for development as a novel anticancer drug.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping