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Dual‐Acting Diether Derivatives of Piperidine and Homopiperidine with Histamine H 3 Receptor Antagonistic and Anticholinesterase Activity
Author(s) -
Bajda Marek,
Kuder Kamil J.,
Łażewska Dorota,
KiećKoowicz Katarzyna,
Więckowska Anna,
Ignasik Michalina,
Guzior Natalia,
Jończyk Jakub,
Malawska Barbara
Publication year - 2012
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201200018
Subject(s) - butyrylcholinesterase , acetylcholinesterase , chemistry , histamine , stereochemistry , piperidine , histamine receptor , aché , receptor , enzyme , potency , biochemistry , in vitro , pharmacology , biology , antagonist
The study presents novel biological properties of diether derivatives of homo‐ or substituted piperidine ligands of the histamine H 3 receptor. The compounds were evaluated for their inhibitory potency against acetylcholinesterase (AChE) from the electric eel and butyrylcholinesterase (BuChE) from horse serum. The most interesting multifunctional compound 13 displayed high affinity for the cloned h H 3 R ( K i = 3.48 nM) and moderate inhibitory potency against both enzymes (IC 50 AChE = 7.91 µM and BuChE = 4.97 µM). Molecular modeling studies revealed interactions with key amino acid residues in the homology model of histamine H 3 receptor ligands, as well as the binding model for AChE and BuChE in the catalytic and peripheral active sites.