title: Novel tacrine analogs as potential cholinesterase inhibitors in Alzheimer's disease.
abstract: Acetylcholinesterase inhibitors (AChEIs) are used for the treatment of Alzheimer's disease (AD). The increase in ACh levels ameliorates the symptoms of the disease. Tacrine is the first clinically approved drug as AChEI used in the treatment of AD. In this paper, we synthesized new tacrine analogs to act on catalytic and peripheral sites of AChE. Their inhibitory activity was evaluated. All novel compounds except 7a showed promising results toward AChE. Two compounds, 10b and 11b, are more potent than tacrine. Furthermore, molecular-modeling studies were performed for these two compounds to rationalize the obtained pharmacological activity. Moreover, various drug-likeness properties of the new compounds were predicted.
authors.affiliation: Faculty of Pharmacy, Pharmaceutical Organic Chemistry Department, Cairo University, Cairo, Egypt.
authors.forename: Afaf
authors.initials: A
authors.lastname: El-Malah
authors.forename: Ehab M
authors.initials: EM
authors.lastname: Gedawy
authors.forename: Asmaa E
authors.initials: AE
authors.lastname: Kassab
authors.forename: Rania M Abdel
authors.initials: RM
authors.lastname: Salam
mesh_terms: D000110:Acetylcholinesterase / Q000302:isolation & purification / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D004593:Electrophorus / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D013619:Tacrine; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Alzheimer's disease; Drug-likeness; Molecular-modeling; Tacrine