Abstract

Tacrine-huperzine A hybrids (huprines) are a new class of very potent and selective acetylcholinesterase (AChE) inhibitors. Huprines were designed from tacrine and (-)-huperzine A through a conjunctive approach. They combine the 4-aminoquinoline substructure of tacrine with the carbobicyclic substructure of (-)-huperzine A. Structural variations on several parts of a lead structure have allowed to complete a structure-activity relationship exploration of this new structural family and have led to several huprines more active than other known AChE inhibitors.

Keywords: Tacrine-huperzine A hybrids (huprines), acetylcholinesterase (AChE) inhibitors, tacrine, (-)-huperzine A, amyloid peptide, amyloid precursor proteine, Acetylcholinesterase, Torpedo Californica Acetylcholinesterase