Dual-Acting Diether Derivatives of Piperidine and Homopiperidine with Histamine H3 Receptor Antagonistic and Anticholinesterase Activity

被引：32

作者：

Bajda, Marek ^{[1
]}

Kuder, Kamil J. ^{[2
]}

Lazewska, Dorota ^{[2
]}

Kiec-Kononowicz, Katarzyna ^{[2
]}

Wieckowska, Anna ^{[1
]}

Ignasik, Michalina ^{[1
]}

Guzior, Natalia ^{[1
]}

Jonczyk, Jakub ^{[1
]}

Malawska, Barbara ^{[1
]}

机构：

[1] Jagiellonian Univ, Dept Physicochem Drug Anal, Chair Pharmaceut Chem, Fac Pharm,Med Coll, PL-30688 Krakow, Poland

[2] Jagiellonian Univ, Dept Technol & Biotechnol Drugs, Fac Pharm, Coll Med, PL-30688 Krakow, Poland

来源：

ARCHIV DER PHARMAZIE | 2012年 / 345卷 / 08期

关键词：

Acetylcholinesterase inhibitors; Butyrylcholinesterase inhibitors; Derivatives of piperidine and homopiperidine; Histamine H3 receptor; Multifunctional ligands; Non-imidazole ligands of H3 receptor; TARGET-DIRECTED LIGANDS; H-3; RECEPTOR; ALZHEIMERS-DISEASE; DRUG DISCOVERY; IN-VITRO; MULTIPLE LIGANDS; ACETYLCHOLINESTERASE; MECHANISMS; INHIBITORS; BRAIN;

D O I：

10.1002/ardp.201200018

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The study presents novel biological properties of diether derivatives of homo- or substituted piperidine ligands of the histamine H3 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 hH3R (Ki?=?3.48?nM) and moderate inhibitory potency against both enzymes (IC50 AChE?=?7.91?mu M and BuChE?=?4.97?mu M). Molecular modeling studies revealed interactions with key amino acid residues in the homology model of histamine H3 receptor ligands, as well as the binding model for AChE and BuChE in the catalytic and peripheral active sites.

引用

页码：591 / 597

页数：7

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