New Disaccharide-Based Ether Lipids as SK3 Ion Channel Inhibitors

International audienceThe SK3 potassium channel is involved in the development ofbone metastasis and in the settlement of cancer cells in Ca2+-rich environments. Ohmline, which is a lactose-based glyceroetherlipid, is a lead compound that decreases SK3 channel activityand consequently limits the migration of SK3-expressingcells. Herein we report the synthesis of three new ohmline analoguesin which the connection of the disaccharide moieties(1!6 versus 1!4) and the stereochemistry of the glycosyllinkage was studied. Compound 2 [3-(hexadecyloxy)-2-methoxypropyl-6-O-a-d-glucopyranosyl-b-d-galactopyranoside], whichpossesses an a-glucopyranosyl-(1!6)-b-galactopyranosylmoiety, was found to decrease SK3 current amplitude (70% inhibitionat 10 mm), displace SK3 protein outside caveolae, anddecrease constitutive Ca2+ entry (50% inhibition at 300 nm)and SK3-dependent cell migration (30% at 300 nm) at a levelclose to that of the benchmark compound ohmline. Compound2, which decreases the activity of SK3 channel (but notSK2 channel), is a new drug candidate to reduce cancer cell migrationand to prevent bone metastasis

High-yielding microwave-assisted synthesis of triazole-linked glycodendrimers by copper-catalyzed [3+2] cycloaddition

A facile and high-yielding synthesis of multivalent 1,4-disubstituted 1,2,3-triazole-linked glycodendrimers is described. Azido carbohydrates are linked by a CuI-catalyzed [3+2] cycloaddition reaction to dendritic acetylenes using microwave irradiation