Privileged multi-target directed propargyl-tacrines combining cholinesterase and monoamine oxidase inhibition activities

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F22%3A50019448" target="_blank" >RIV/62690094:18470/22:50019448 - isvavai.cz</a>

Alternative codes found

RIV/00179906:_____/22:10448547 RIV/60162694:G44__/23:00558337 RIV/00216208:11150/22:10448547

Result on the web

<a href="https://www.tandfonline.com/doi/full/10.1080/14756366.2022.2122054" target="_blank" >https://www.tandfonline.com/doi/full/10.1080/14756366.2022.2122054</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/14756366.2022.2122054" target="_blank" >10.1080/14756366.2022.2122054</a>

Result language

angličtina

Original language name

Privileged multi-target directed propargyl-tacrines combining cholinesterase and monoamine oxidase inhibition activities

Original language description

Twenty-four novel compounds bearing tetrahydroacridine and N-propargyl moieties have been designed, synthesised, and evaluated in vitro for their anti-cholinesterase and anti-monoamine oxidase activities. Propargyltacrine 23 (IC50 = 21 nM) was the most potent acetylcholinesterase (AChE) inhibitor, compound 20 (IC50 = 78 nM) showed the best inhibitory human butyrylcholinesterase (hBChE) profile, and ligand 21 afforded equipotent and significant values on both ChEs (human AChE [hAChE]: IC50 = 0.095 ± 0.001 µM; hBChE: IC50 = 0.093 ± 0.003 µM). Regarding MAO inhibition, compounds 7, 15, and 25 demonstrated the highest inhibitory potential towards hMAO-B (IC50 = 163, 40, and 170 nM, respectively). In all, compounds 7, 15, 20, 21, 23, and 25 exhibiting the most balanced pharmacological profile, were submitted to permeability and cell viability tests. As a result, 7-phenoxy-N-(prop-2-yn-1-yl)-1,2,3,4-tetrahydroacridin-9-amine hydrochloride (15) has been identified as a permeable agent that shows a balanced pharmacological profile [IC50 (hAChE) = 1.472 ± 0.024 µM; IC50 (hBChE) = 0.659 ± 0.077 µM; IC50 (hMAO-B) = 40.39 ± 5.98 nM], and consequently, as a new hit-ligand that deserves further investigation, in particular in vivo analyses, as the preliminary cell viability test results reported here suggest that this is a relatively safe therapeutic agent.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30107 - Medicinal chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of enzyme inhibition and medicinal chemistry

ISSN

1475-6366

e-ISSN

1475-6374

Volume of the periodical

37

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

2605-2620

UT code for WoS article

000859610700001

EID of the result in the Scopus database

2-s2.0-85138287767