Tacrine based human cholinesterase inhibitors: synthesis of peptidic-tethered derivatives and their effect on potency and selectivity.
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.
Butini
Stefania
S
European Research Centre for Drug Discovery and Development (NatSynDrugs), Via Aldo Moro 2, 53100 Siena, Italy.
Guarino
Egeria
E
Campiani
Giuseppe
G
Brindisi
Margherita
M
Coccone
Salvatore Sanna
SS
Fiorini
Isabella
I
Novellino
Ettore
E
Belinskaya
Tatyana
T
Saxena
Ashima
A
Gemma
Sandra
S
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
D002800:Cholinesterase Inhibitors; D010455:Peptides; D013619:Tacrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase