Caliandro_2018_J.Enzyme.Inhib.Med.Chem_33_794

Reference

Title : Kinetic and structural studies on the interactions of Torpedo californica acetylcholinesterase with two donepezil-like rigid analogues - Caliandro_2018_J.Enzyme.Inhib.Med.Chem_33_794
Author(s) : Caliandro R , Pesaresi A , Cariati L , Procopio A , Oliverio M , Lamba D
Ref : J Enzyme Inhib Med Chem , 33 :794 , 2018
Abstract : Acetylcholinesterase inhibitors were introduced for the symptomatic treatment of Alzheimer's disease (AD). Among the currently approved inhibitors, donepezil (DNP) is one of the most preferred choices in AD therapy. The X-ray crystal structures of Torpedo californica AChE in complex with two novel rigid DNP-like analogs, compounds 1 and 2, have been determined. Kinetic studies indicated that compounds 1 and 2 show a mixed-type inhibition against TcAChE, with Ki values of 11.12 +/- 2.88 and 29.86 +/- 1.12 nM, respectively. The DNP rigidification results in a likely entropy-enthalpy compensation with solvation effects contributing primarily to AChE binding affinity. Molecular docking evidenced the molecular basis for the binding of compounds 1 and 2 to the active site of beta-secretase-1. Overall, these simplified DNP derivatives may represent new structural templates for the design of lead compounds for a more effective therapeutic strategy against AD by foreseeing a dual AChE and BACE-1 inhibitory activity.
ESTHER : Caliandro_2018_J.Enzyme.Inhib.Med.Chem_33_794
PubMedSearch : Caliandro_2018_J.Enzyme.Inhib.Med.Chem_33_794
PubMedID: 29651884
Gene_locus related to this paper: torca-ACHE

Related information

Gene_locus related to this paper: torca-ACHE

Citations formats

Caliandro R, Pesaresi A, Cariati L, Procopio A, Oliverio M, Lamba D (2018)
Kinetic and structural studies on the interactions of Torpedo californica acetylcholinesterase with two donepezil-like rigid analogues
J Enzyme Inhib Med Chem 33 :794

Caliandro R, Pesaresi A, Cariati L, Procopio A, Oliverio M, Lamba D (2018)
J Enzyme Inhib Med Chem 33 :794