期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 186, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.111854
关键词
Ca2+-activated K+ channels; SK3; Breast cancer; Cell migration; Amphiphilic compounds; Tetrahydropyridine derivatives
资金
- Roseau Canaux Ioniques of the Canceropole Grand Ouest
- Ligue Contre le Cancer
- University of Tours
- Region Centre Val de Loire
- INSERM
- Ministere de l'enseignement superieur et de la recherche
Small Conductance Calcium (Ca2+)-activated potassium (K+) channels (SKCa) are now proved to be involved in many cancer cell behaviors such as proliferation or migration. The SK3 channel isoform was particularly described in breast cancer where it can be associated with the Orail Ca2+ channel to form a complex that regulates the Ca2+ homeostasis during tumor development and acts as a potent mediator of bone metastases development in vivo. Until now, very few specific blockers of Orail and/or SK3 have been developed as potential anti-metastatic compounds. In this study, we illustrated the synthesis of new families of lipophilic pyridine and tetrahydropyridine derivatives designed as potential modulators of SK3 channel. The toxicity of the newly synthesized compounds and their migration effects were evaluated on the breast cancer cell line MDA-MB-435s. Two molecules (7a and 10c) demonstrated a significant decrease in the SK3 channel-dependent migration as well as the SK3/Orai1-related Ca2+ entry. Current measurements showed that these compounds are more likely SK3-selective. Taken all together these results suggest that such molecules could be considered as promising anti-metastatic drugs in breast cancer. (C) 2019 Published by Elsevier Masson SAS.
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