Development of pyrene-based fluorescent ether lipid as inhibitor of SK3 ion channels - Université de Bretagne Occidentale Access content directly
Journal Articles European Journal of Medicinal Chemistry Year : 2021

Development of pyrene-based fluorescent ether lipid as inhibitor of SK3 ion channels

Abstract

We report the synthesis of three bioactive pyrene-based fluorescent analogues of Ohmline which is the most efficient and selective inhibitor of SK3 ion channel. The interaction of these Ohmline-pyrene (OP1-3) with liposomes of different composition reveals that only OP2 and OP3 are readily integrated into liposomes. Fluorescence measurements indicate that, depending on their concentration, OP2 and OP3 exist either as monomer or as a mixture of monomer and excimers within the liposome bilayer. Among the three Ohmline Pyrene compounds (OP1-3) only OP2 is able to reduce SK3 currents and is the first efficient fluorescent modulator of SK3 channel as revealed by patch clamp measurements (- 71.3 ± 13.3% at 10 mM) and by its inhibition of SK3-dependent cancer cell migration at (32.5% ± 4.8% at 1 mM). We also report the first fluorescence study on living breast cancer cells (MDA-MB-231) showing that OP2 is rapidly integrated in bio-membranes followed by cell internalization.
Nous décrivons la synthèse d’analogues de l’Ohmline comportant au niveau de la partie lipidique une sonde fluorescente de type pyrène. Nous montrons que l’un d’entre eux (le composé OP2) est capable de réduire les courants potassiques SK3 de 71% et de réduire la migration cellulaire SK3-dépendante de 32%. Il s’agit, à notre connaissance, du premier inhibiteur des canaux ioniques SK3 de nature amphiphile et fluorescent.
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hal-02997273 , version 1 (17-10-2022)

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Alicia Bauduin, Marion Papin, Aurélie Chantôme, Hélène Couthon, Laure Burel-Deschamps, et al.. Development of pyrene-based fluorescent ether lipid as inhibitor of SK3 ion channels. European Journal of Medicinal Chemistry, 2021, 209, pp.112894. ⟨10.1016/j.ejmech.2020.112894⟩. ⟨hal-02997273⟩
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