Chen, Xinyu and Tikhonova, Irina G. and Decker, Michael (2011) Probing the mid-gorge of cholinesterases with spacer-modified bivalent quinazolinimines leads to highly potent and selective butyrylcholinesterase inhibitors. BIOORGANIC & MEDICINAL CHEMISTRY, 19 (3). pp. 1222-1235. ISSN 0968-0896, 1464-3391
Full text not available from this repository. (Request a copy)Abstract
The spacer structure of homobivalent quinazolinimes acting as potent acetyl-(AChE)- and butyrylcholinesterase (BChE) inhibitors was chemically modified introducing tertiary amine and acyl-amide moieties, and the activities at both ChEs were evaluated. Molecular docking was applied to explain the data and probe the capacity of the mid-gorge site of both ChEs. The novel spacer structures considerably alter the biological profile of bivalent quinazolinimines with regard to both inhibitory activity and selectivity. Mutual interaction of binding to the various sites of the enzymes was further investigated by applying also different spacer lengths and ring sizes of the alicycle of the tricyclic quinazolinimines. In order to achieve selectivity toward BChE and to improve inhibitory activities, the spacer structure was optimized and identified a highly potent and selective BChE inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACETYLCHOLINESTERASE INHIBITORS; HETERO-BIVALENT; RATIONAL DESIGN; ACTIVE-SITE; BINDING; LIGANDS; FLUCTUATIONS; RECEPTORS; SALTS; Alzheimer's disease; Cholinesterase; Molecular docking; Bivalent inhibitors; Quinazolinimines |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jun 2020 07:27 |
| Last Modified: | 26 Jun 2020 07:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21305 |
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