title: Synthesis, molecular modeling and evaluation of novel N'-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone derivatives as dual inhibitors for cholinesterases and Aβ aggregation.
abstract: To develop new drugs for treatment of Alzheimer's disease, a group of N'-2-(4-Benzylpiperidin-/piperazin-1-yl)acylhydrazones was designed, synthesized and tested for their ability to inhibit acetylcholinesterase, butyrylcholinesterase and aggregation of amyloid beta peptides (1-40, 1-42 and 1-40_1-42). The enzyme inhibition assay results indicated that compounds moderately inhibit both acetylcholinesterase and butyrylcholinesterase. β-Amyloid aggregation results showed that all compounds exhibited remarkable Aβ fibril aggregation inhibition activity with a nearly similar potential as the reference compound rifampicin, which makes them promising anti-Alzheimer drug candidates. Docking experiments were carried out with the aim to understand the interactions of the most active compounds with the active site of the cholinesterase enzymes.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Başkent University, Ankara 06530, Turkey.
authors.forename: Eda
authors.initials: E
authors.lastname: Özturan Özer
authors.forename: Oya Unsal
authors.initials: OU
authors.lastname: Tan
authors.forename: Keriman
authors.initials: K
authors.lastname: Ozadali
authors.forename: Tuba
authors.initials: T
authors.lastname: Küçükkılınç
authors.forename: Ayla
authors.initials: A
authors.lastname: Balkan
authors.forename: Gülberk
authors.initials: G
authors.lastname: Uçar
mesh_terms: D000215:Acylation; D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D001593:Benzyl Compounds; D002800:Cholinesterase Inhibitors; D006835:Hydrazones; D010879:Piperazines