title: Dual-acting diether derivatives of piperidine and homopiperidine with histamine H(3) receptor antagonistic and anticholinesterase activity.
abstract: 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 hH(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.
authors.affiliation: Department of Physicochemical Drug Analysis, Chair of Pharmaceutical Chemistry, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bajda
authors.forename: Kamil J
authors.initials: KJ
authors.lastname: Kuder
authors.forename: Dorota
authors.initials: D
authors.lastname: Lażewska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kieć-Kononowicz
authors.forename: Anna
authors.initials: A
authors.lastname: Więckowska
authors.forename: Michalina
authors.initials: M
authors.lastname: Ignasik
authors.forename: Natalia
authors.initials: N
authors.lastname: Guzior
authors.forename: Jakub
authors.initials: J
authors.lastname: Jończyk
authors.forename: Barbara
authors.initials: B
authors.lastname: Malawska
mesh_terms: D000818:Animals; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004593:Electrophorus; D004987:Ethers / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006633:Histamine Antagonists / Q000737:chemistry / Q000494:pharmacology*; D006736:Horses; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D004987:Ethers; D006633:Histamine Antagonists; D010880:Piperidines