Darras, Fouad H. and Kling, Beata and Heilmann, Joerg and Decker, Michael (2012) Neuroprotective Tri- and Tetracyclic BChE Inhibitors Releasing Reversible Inhibitors upon Carbamate Transfer. ACS MEDICINAL CHEMISTRY LETTERS, 3 (11). pp. 914-919. ISSN 1948-5875,
Full text not available from this repository. (Request a copy)Abstract
Tri- and tetracyclic nitrogen-bridgehead compounds were designed and synthesized to yield micromolar cholinesterase (chE), inhibitors. Structure-activity relationships identified potent compounds with butyrylcholinesterase selectivity. These compounds were selected as starting points for the design and synthesis of carbamate-based (pseudo)irreversible inhibitors. Compounds with superior inhibitory activity and selectivity were obtained and kinetically characterized also with regard to the velocity of enzyme carbamoylation. Structural elements were identified and introduced that additionally showed neuroprotective properties on a hippocampal neuronal cell line (HT 22) after glutamate induced intracellular reactive oxygen species generation. We have identified potent and selective pseudoirreversible butyrylcholinesterase inhibitors that release reversible inhibitors with neuroprotective properties after carbamate transfer to the active site of cholinesterases.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ALZHEIMERS-DISEASE; OXIDATIVE STRESS; HYBRID MOLECULES; NEURONAL CELLS; BUTYRYLCHOLINESTERASE; DESIGN; ACETYLCHOLINESTERASE; QUINAZOLINIMINES; RIVASTIGMINE; SELECTIVITY; Alzheimer's disease; butyrylcholinesterase; carbamates; neuroprotection |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Biology (Prof. Heilmann) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 May 2020 04:57 |
| Last Modified: | 05 May 2020 04:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17860 |
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