Alonso_2005_Bioorg.Med.Chem_13_6588

Reference

Title : Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE - Alonso_2005_Bioorg.Med.Chem_13_6588
Author(s) : Alonso D , Dorronsoro I , Rubio L , Munoz P , Garcia-Palomero E , del Monte M , Bidon-Chanal A , Orozco M , Luque FJ , Castro A , Medina M , Martinez A
Ref : Bioorganic & Medicinal Chemistry , 13 :6588 , 2005
Abstract :

A new series of donepezil-tacrine hybrid related derivatives have been synthesised as dual acetylcholinesterase inhibitors that could bind simultaneously to the peripheral and catalytic sites of the enzyme. These new hybrids combined a tacrine, 6-chlorotacrine or acridine unit as catalytic binding site and indanone (the heterocycle present in donepezil) or phthalimide moiety as peripheral binding site of the enzyme, connected through a different linker tether length. One of the synthesised compounds emerged as a potent and selective AChE inhibitor, which is able to displace propidium in a competition assay. These results seem to confirm the ability of this inhibitor to bind simultaneously to both sites of the enzyme and make it a promising lead for developing disease-modifying drugs for the future treatment of Alzheimer's disease. To gain insight into the molecular determinants that modulate the inhibitory activity of these compounds, a molecular modelling study was performed to explore their binding to the enzyme.

PubMedSearch : Alonso_2005_Bioorg.Med.Chem_13_6588
PubMedID: 16230018

Related information

Inhibitor SCHEMBL1532301

Citations formats

Alonso D, Dorronsoro I, Rubio L, Munoz P, Garcia-Palomero E, del Monte M, Bidon-Chanal A, Orozco M, Luque FJ, Castro A, Medina M, Martinez A (2005)
Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE
Bioorganic & Medicinal Chemistry 13 :6588

Alonso D, Dorronsoro I, Rubio L, Munoz P, Garcia-Palomero E, del Monte M, Bidon-Chanal A, Orozco M, Luque FJ, Castro A, Medina M, Martinez A (2005)
Bioorganic & Medicinal Chemistry 13 :6588