Jump to main content
Jump to site search

Issue 11, 2012
Previous Article Next Article

Glyco-Phospho-Glycero Ether Lipids (GPGEL): synthesis and evaluation as small conductance Ca2+-activated K+ channel (SK3) inhibitors

Author affiliations

Abstract

The SK3 channel, a member of the small conductance calcium-dependent potassium channels (SKCa), plays a central role with respect to the motility of highly metastatic cancerous cells (e.g. MDA-MB435s – breast cancer cell). Edelfosine, an ether lipid derivative, is able to partially inhibit this channel activity and thus reduce the SK3-dependent cell motility, but, due to its toxicity, analogues of this compound were highly desired. Ohmline, an edelfosine analogue that possesses a lactose unit in its polar domain, was the first efficient and non-toxic SK3 inhibitor that exhibits an amphiphilic structure. In the present work, we have modified the polar head of Ohmline by placing a disubstituted phosphate group between a disaccharide unit (lactose, maltose, and melibiose) and the glycerol ether-lipid moiety. It was first observed that this modification increases the water solubility of these compounds. All these novel compounds are efficient SK3 channel inhibitors with an activity comparable to Ohmline (patch-clamp measurements). These compounds are also able to reduce the SK3-dependent cell motility with similar efficacies to Ohmline. In a broader perspective it is shown that the presence of one anionic charge (coming from the presence of a phosphate group) in the polar head group does not alter the SK3 channel inhibition and provides insights into the future development of a class of migration-targeted anticancer agents.

Graphical abstract: Glyco-Phospho-Glycero Ether Lipids (GPGEL): synthesis and evaluation as small conductance Ca2+-activated K+ channel (SK3) inhibitors

Back to tab navigation

Supplementary files

Publication details

The article was received on 23 Jul 2012, accepted on 12 Sep 2012 and first published on 14 Sep 2012


Article type: Concise Article
DOI: 10.1039/C2MD20207G
Med. Chem. Commun., 2012,3, 1471-1478

  •   Request permissions

    Glyco-Phospho-Glycero Ether Lipids (GPGEL): synthesis and evaluation as small conductance Ca2+-activated K+ channel (SK3) inhibitors

    C. M. Sevrain, J. Haelters, A. Chantôme, H. Couthon-Gourvès, A. Girault, C. Vandier and P. Jaffrès, Med. Chem. Commun., 2012, 3, 1471
    DOI: 10.1039/C2MD20207G

Search articles by author

Spotlight

Advertisements