GIST Scholar
College of Life Sciences and Medical Engineering
Department of Life Sciences
1. Journal Articles
Potent Suppressive Effects of 1-Piperidinylimidazole Based Novel P2X7 Receptor Antagonists on Cancer Cell Migration and Invasion
- Type
- Article
- Citation
- Journal of Medicinal Chemistry, v.59, no.16, pp.7410 - 7430
- Issued Date
- 2016-07
- Abstract
- The P2X7 receptor (P2X7R) has been reported as a key mediator in inflammatory processes and cancer invasion/metastasis. In this study, we report the discovery of novel P2X7R antagonists and their functional activities as potential antimetastatic agents. Modifications of the hydantoin core-skeleton and the side chain substituents of the P2X7R antagonist 7 were performed. The structure activity relationships (SAR) and optimization demonstrated the importance of the sulfonyl group at the R-1 position and the substituted position and overall size of R-2 for P2X7R antagonism. The optimized novel analogues displayed potent P2X7 receptor antagonism (IC50 = 0.11-112 nM) along with significant suppressive effects on IL-1 beta release (IC50 = 0.32-210 nM). Moreover, representative antagonists (12g, 13k, and 17d) with imidazole and uracil core skeletons significantly inhibited the invasion of MDA-MB-231 triple negative breast cancer cells and cancer cell migration in a zebrafish xenograft model, suggesting the potential therapeutic application of these novel P2X7 antagonists to block metastatic cancer.
- Publisher
- American Chemical Society
- ISSN
- 0022-2623
- Appears in Collections:
- Department of Life Sciences > 1. Journal Articles
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