title: Tacrine based human cholinesterase inhibitors: synthesis of peptidic-tethered derivatives and their effect on potency and selectivity.
abstract: Tacrine based reversible inhibitors of cholinesterases (ChEIs) containing peptidic tethers were synthesized to interact with specific regions at the gorge level, and their potency was determined with human (h) acetylcholinesterase and butyrylcholinesterase. Analogues 3i,j and 3l,m were identified as promising hits and may pave the way for the development of a new series of tacrine based enzyme selective hChEIs.
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Butini
authors.forename: Egeria
authors.initials: E
authors.lastname: Guarino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campiani
authors.forename: Margherita
authors.initials: M
authors.lastname: Brindisi
authors.forename: Salvatore Sanna
authors.initials: SS
authors.lastname: Coccone
authors.forename: Isabella
authors.initials: I
authors.lastname: Fiorini
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Tatyana
authors.initials: T
authors.lastname: Belinskaya
authors.forename: Ashima
authors.initials: A
authors.lastname: Saxena
authors.forename: Sandra
authors.initials: S
authors.lastname: Gemma
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D010455:Peptides; D013619:Tacrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase