PUBLICATION
Tanshinone-IIA-Based Analogs of Imidazole Alkaloid Act as Potent Inhibitors to Block Breast Cancer Invasion and Metastasis in vivo
- Authors
- Wu, Q., Zheng, K., Huang, X., Li, L., Mei, W.
- ID
- ZDB-PUB-181107-9
- Date
- 2018
- Source
- Journal of medicinal chemistry 61(23): 10488-10501 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Abietanes/chemistry*
- Alkaloids/chemistry*
- Animals
- Antineoplastic Agents, Phytogenic/chemistry*
- Antineoplastic Agents, Phytogenic/pharmacology*
- Apoptosis/drug effects
- Breast Neoplasms/pathology*
- Cell Line, Tumor
- Cell Movement/drug effects
- Humans
- Imidazoles/chemistry*
- Imidazoles/pharmacology*
- Models, Molecular
- Molecular Conformation
- Neoplasm Invasiveness
- Neoplasm Metastasis
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 30398868 Full text @ J. Med. Chem.
Citation
Wu, Q., Zheng, K., Huang, X., Li, L., Mei, W. (2018) Tanshinone-IIA-Based Analogs of Imidazole Alkaloid Act as Potent Inhibitors to Block Breast Cancer Invasion and Metastasis in vivo. Journal of medicinal chemistry. 61(23):10488-10501.
Abstract
Tanshinone-IIA (Tan-IIA), a primary active component extracted from commonly used Chinese herbal, Salvia miltiorrhiza (Danshen), is considered as a potential inhibitor against tumor-cell proliferation. However, the potential application of Tan-IIA is hindered by its poor water solubility and low bioavailability. In this work, an imidazole moiety was linked to the skeleton of Tan-IIA to enhance its antitumor activity. A series of Tan-IIA-based analogs TA01-TA12 were synthesized, and their inhibitory activities against the migration and invasion of MDA-MB-231 cells were investigated. All compounds, particularly TA12, markedly inhibited the proliferation, migration and invasion of MDA-MB-231cells. TA12 also prominently blocked cancer-cell metastasis in blood vessels and surrounding tissues in zebrafish xenograft model. Further studies showed that the mechanisms may involve S-phase arrest pathway, which was probably caused by inducing reactive oxygen species production and activating DNA damage. These results indicated that the Tan-IIA-based analogs of imidazole derivates can act as potent anti-metastasis agents.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping