Scheme 7.

Pharmacophore of azo dyes and various potent inhibitors superposed to pharmacophore model of VGLUTs. The pharmacophore model allow the 3D representation of key features for potent VGLUT inhibitory activity. This model was generated based on the activity of various ligands (trypan blue (EC50 = 50 nM), Evans blue (EC50 = 90 nM), Brillant Yellow (EC50 = 15 nM, Chicago Blue Sky (EC50 = 330 nM), Direct violet 51 (EC50 = 148 nM), Chrysophenin (EC50 = 27 nM), four 2,4-dicarboxy-quinolines (EC50 = 41 μM; 64 μM; 167 μM; 288 μM), four monoazoic dyes (EC50 = 1.6 μM; 3.3 μM; 25 μM; 40 μM)). Structural key requirements to obtain a potent VGLUT inhibitor are represented by color spheres (green = H bond donor, slight blue = aromatic moiety, dark blue = negative charge); the putative ligand/VGLUT steric bump are represented by exclusion gray spheres