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N-propargylpiperidines with naphthalene-2-carboxamide or naphthalene-2- sulfonamide moietiesKošak, Urban ...In the brains of patients with Alzheimer's disease, the enzymatic activities of butyrycholinesterase (BChE) and monoamine oxidase B (MAO-B) are increased. While BChE is a viable therapeutic target ... for alleviation of symptoms caused by cholinergic hypofunction, MAO-B is a potential therapeutic target for prevention of neurodegeneration in Alzheimer's disease. Starting with piperidine-based selective human (h)BChE inhibitors and propargylamine-based MAO inhibitors, we have designed, synthesized and biochemically evaluated a series of N-propargylpiperidines. All of these compounds inhibited hBChE with good selectivity over the related enzyme, acetylcholinesterase, and crossed the blood-brain barrier in a parallel artificial membrane permeation assay. The crystal structure of one of the inhibitors (compound 3) in complex with hBChE revealed its binding mode. Three compounds (4, 5, 6) showed concomitant inhibition of MAO-B. Additionally, the most potent hBChE inhibitor 7 and dual BChE and MAO-B inhibitor 6 were non-cytotoxic and protected neuronal SH-SY5Y cells from toxic amyloid ß-peptide species.Source: Bioorganic & Medicinal Chemistry. - ISSN 0968-0896 (Vol. 25, iss. 2, 2017, str. 633-645)Type of material - article, component part ; adult, seriousPublish date - 2017Language - englishCOBISS.SI-ID - 4248177
Author
Košak, Urban |
Knez, Damijan, farmacevt |
Coquelle, Nicolas |
Brus, Boris |
Pišlar, Anja |
Nachon, Florian |
Brazzolotto, Xavier |
Kos, Janko, 1959- |
Colletier, Jacques-Philippe |
Gobec, Stanislav, 1970-
Topics
Alzheimerjeva bolezen |
multitarget-directed ligands |
butyrylcholinesterase inhibitors |
AO-B inhibitors |
acetylcholinesterase
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Košak, Urban | 33908 |
Knez, Damijan, farmacevt | 36438 |
Coquelle, Nicolas | |
Brus, Boris | 34508 |
Pišlar, Anja | 32035 |
Nachon, Florian | |
Brazzolotto, Xavier | |
Kos, Janko, 1959- | 04648 |
Colletier, Jacques-Philippe | |
Gobec, Stanislav, 1970- | 15284 |
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