Gabr_2018_Bioorg.Med.Chem.Lett_28_2910

Reference

Title : Structure-based design, synthesis, and evaluation of structurally rigid donepezil analogues as dual AChE and BACE-1 inhibitors - Gabr_2018_Bioorg.Med.Chem.Lett_28_2910
Author(s) : Gabr MT , Abdel-Raziq MS
Ref : Bioorganic & Medicinal Chemistry Lett , 28 :2910 , 2018
Abstract :

A new series of structurally rigid donepezil analogues was designed, synthesized and evaluated as potential multi-target-directed ligands (MTDLs) against neurodegenerative diseases. The investigated compounds 10-13 displayed dual AChE and BACE-1 inhibitory activities in comparison to donepezil, the FDA-approved drug. The hybrid compound 13 bearing 2-aminoquinoline scaffold exhibited potent AChE inhibition (IC50 value of 14.7nM) and BACE-1 inhibition (IC50 value of 13.1nM). Molecular modeling studies were employed to reveal potential dual binding mode of 13 to AChE and BACE-1. The effect of the investigated compounds on the viability of SH-SY5Y neuroblastoma cells and their ability to cross the blood-brain barrier (BBB) in PAMPA-BBB assay were further studied.

PubMedSearch : Gabr_2018_Bioorg.Med.Chem.Lett_28_2910
PubMedID: 30017317

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Citations formats

Gabr MT, Abdel-Raziq MS (2018)
Structure-based design, synthesis, and evaluation of structurally rigid donepezil analogues as dual AChE and BACE-1 inhibitors
Bioorganic & Medicinal Chemistry Lett 28 :2910

Gabr MT, Abdel-Raziq MS (2018)
Bioorganic & Medicinal Chemistry Lett 28 :2910