Darras, Fouad H. and Kling, Beata and Sawatzky, Edgar and Heilmann, Joerg and Decker, Michael (2014) Cyclic acyl guanidines bearing carbamate moieties allow potent and dirigible cholinesterase inhibition of either acetyl- or butyrylcholinesterase. BIOORGANIC & MEDICINAL CHEMISTRY, 22 (17). pp. 5020-5034. ISSN 0968-0896, 1464-3391
Full text not available from this repository. (Request a copy)Abstract
A series of cyclic acyl guanidine with carbamate moieties have been synthesized and evaluated in vitro for their AChE and BChE inhibitory activities. Structure-activity relationships identified compound 23 as a nanomolar and selective BChE inhibitor, while compound 32 exhibited nanomolar and selective AChE inhibition, selectivity depending on both the structure of the carbamate substituent as well as the position of guanidines-N substitution. The velocity of enzyme carbamoylation was analyzed and showed similar behavior to physostigmine. Phenolic compounds formed after carbamate transfer to the active site of cholinesterases showed additional neuroprotective properties on a hippocampal neuronal cell line (HT-22) after glutamate-induced intracellular reactive oxygen species generation. (C) 2014 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NITROGEN-BRIDGEHEAD COMPOUNDS; NEURONAL CELL-LINE; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; HUMAN ACETYLCHOLINESTERASE; ASSAY; QUINAZOLINIMINES; FLUORESCEIN; ANTIOXIDANT; SELECTIVITY; Alzheimer's disease; Cholinesterase inhibitors; Pseudoirreversible inhibition; Neuroprotection; Acyl guanidines |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Aug 2019 11:29 |
| Last Modified: | 29 Aug 2019 11:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9679 |
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