Development of tacrine clusters as positively cooperative systems for the inhibition of acetylcholinesterase

The synthesis of four tetra-tacrine clusters where the tacrine binding units are attached to a central scaffold via linkers of variable lengths is described. The multivalent inhibition potencies for the tacrine clusters were investigated for the inhibition of acetylcholinesterase. Two of the tacrine clusters displayed a small but significant multivalent inhibition potency in which the binding affinity of each of the tacrine binding units increased up to 3.2 times when they are connected to the central scaffold.

Automated summary

The synthesis of four tetra-tacrine clusters with varying linker lengths attached to a central scaffold was investigated for their multivalent inhibition potencies against acetylcholinesterase. Two of the clusters demonstrated significant binding affinity increases of up to 3.2 times when connected to the central scaffold.