Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

The vesicular acetylcholine transporter (VAChT) is an important target for in vivo imaging of neurodegenerative processes using positron-emission-tomography. So far the development of VAChT radioligands is based on the single known lead compound vesamicol. In this study we investigated a recently published spiroindoline compound class (Sluder et al. 2012), which was suggested to have potential in the development of VAChT ligands. Therefore, we synthesized a small series of spiroindoline derivatives and determined their in vitro binding affinities toward the VAChT. In order to investigate the selectivity, the off-target binding toward 1 and 2 receptors were determined. The compounds possessed VAChT affinities with Ki values in the range of 39 to 376 nM. Binding affinities toward the 1 and 2 receptors are in a similar range indicating that the strong structural difference between the spiroindolines and vesamicol did not improve the selectivity. The observed potential to additionally bind to  receptors let us assume that the herein investigated spiroindolines are not suitable to replace vesamicol as lead compound for the development of VAChT ligands.