Figure 5.

Proposed binding mode of 33 (pink) and 1a (green) at the α7-nAChR orthosteric binding site (PDB ID: 7EKP). The receptor backbone is represented by sky-blue cartoons, and individual residues defining the binding site are colored in gray. π–cation interactions are shown as dashed green lines, while hydrogen bonds are shown as yellow dashed lines. The inner surface of the binding pocket is depicted in gray, lipophilic areas are in yellow, and hydrophilic areas where the H-bond donor is favored are in blue. Superimposition of the docking poses of 33 and 1a reveals the critical H-bonding between the indole moiety of 33 and the distal hydrophilic area of the α7α7 binding site, plausibly responsible for 120 times higher affinity.