Pro-cognitive effect of bis(7)-tacrine as potential therapeutic agent against neurodegenerative disorders
Abstract
The acetylcholinesterase (AChE) structure elucidation has significantly contributed to the development of both novel homo- and heterodimer molecules that are capable of simultaneous binding to both anionic sites of the enzyme. This mostly resulted into improved AChE inhibition potency concurrently affecting other pathological hallmarks of the disease.
In thisregard, bis(7)-tacrine can be considered asthe pioneering molecule. It consists of two tacrine moieties connected via alkylene tether of seven carbon atoms.
In in vitro and in vivo, bis(7)-tacrine revealed interesting multipotent profile capable to affect several enzymes and receptors which are implicated in the pathogenesis of AD. It also became a key structural template in the development of other more potent compounds intended for the therapy of neurodegenerative disorders.