Premium
Novel N ‐allyl/propargyl tetrahydroquinolines: Synthesis via Three‐component Cationic Imino Diels–Alder Reaction, Binding Prediction, and Evaluation as Cholinesterase Inhibitors
Author(s) -
Rodríguez Yeray A.,
Gutiérrez Margarita,
Ramírez David,
AlzateMorales Jans,
Bernal Cristian C.,
Güiza Fausto M.,
Romero Bohórquez Arnold R.
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12773
Subject(s) - chemistry , acetylcholinesterase , cholinesterase , cationic polymerization , docking (animal) , selectivity , propargyl , stereochemistry , active site , enzyme , combinatorial chemistry , biochemistry , organic chemistry , catalysis , biology , pharmacology , medicine , nursing
New N ‐allyl/propargyl 4‐substituted 1,2,3,4‐tetrahydroquinolines derivatives were efficiently synthesized using acid‐catalyzed three components cationic imino Diels–Alder reaction (70–95%). All compounds were tested in vitro as dual acetylcholinesterase and butyryl‐cholinesterase inhibitors and their potential binding modes, and affinity, were predicted by molecular docking and binding free energy calculations (∆G) respectively. The compound 4af ( IC 50 = 72 μ m ) presented the most effective inhibition against acetylcholinesterase despite its poor selectivity ( SI = 2), while the best inhibitory activity on butyryl‐cholinesterase was exhibited by compound 4ae ( IC 50 = 25.58 μ m ) with considerable selectivity ( SI = 0.15). Molecular docking studies indicated that the most active compounds fit in the reported acetylcholinesterase and butyryl‐cholinesterase active sites. Moreover, our computational data indicated a high correlation between the calculated ∆ G and the experimental activity values in both targets.