Synthesis and biological evaluation of fluorescent GAT-ligands based on meso- substituted BODIPY dyes

BODIPY dyes are well known for their outstanding spectroscopic properties and are therefore established in a range of fluorescence based analysis techniques for in vitro as well as for in vivo measurements. For the first time, we designed and synthesized a series of fluorescent ligands for the SLC6 family transporters mGAT1–mGAT4 based on BODIPY dyes as fluorogenic subunits. In the novel series of fluorescent compounds, BODIPY dye subunits are linked with an alkyl chain of three to five carbon atoms that originates from the meso -position of the BODIPY dye to the amino function of different cyclic amines. Screening of these fluorescent probes for their biological activity as GABA uptake inhibitors of mGAT1–mGAT4 revealed ligands with pIC 50 values up to 5.35.