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Novel propargylamine-based inhibitors of cholinesterases and monoamine oxidases: Synthesis, biological evaluation and docking study

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F21%3A10434661" target="_blank" >RIV/00216208:11160/21:10434661 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216275:25310/21:39917725

  • Result on the web

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=3U-mR-rm9K" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=3U-mR-rm9K</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.bioorg.2021.105301" target="_blank" >10.1016/j.bioorg.2021.105301</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Novel propargylamine-based inhibitors of cholinesterases and monoamine oxidases: Synthesis, biological evaluation and docking study

  • Original language description

    A combination of several pharmacophores in one molecule has been successfully used for multi-target-directed ligands (MTDL) design. New propargylamine substituted derivatives combined with salicylic and cinnamic scaffolds were designed and synthesized as potential cholinesterases and monoamine oxidases (MAOs) inhibitors. They were evaluated in vitro for inhibition of acetyl- (AChE) and butyrylcholinesterase (BuChE) using Ellman&apos;s method. All the compounds act as dual inhibitors. Most of the derivatives are stronger inhibitors of AChE, the best activity showed 5-bromo-N-(prop-2-yn-1-yl)salicylamide 1e (IC50 = 8.05 mu M). Carbamates 4-bromo-2-[(prop-2-yn-1-yl)carbamoyl]phenyl ethyl(methyl)carbamate 2d and 2,4-dibromo-6-[(prop-2-yn-1-yl)carbamoyl]phenyl ethyl(methyl)carbamate 2e were selective and the most active for BuChE (25.10 and 26.09 mu M). 4-Bromo-2-[(prop-2-yn-1-ylimino)methyl]phenol 4a was the most potent inhibitor of MAOs (IC50 of 3.95 and approximate to 10 mu M for MAO-B and MAO-A, respectively) along with a balanced inhibition of both cholinesterases being a real MTDL. The mechanism of action was proposed, and binding modes of the hits were studied by molecular docking on human enzymes. Some of the derivatives also exhibited antioxidant properties. In silico prediction of physicochemical parameters affirm that the molecules would be active after oral administration and able to reach brain tissue.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30104 - Pharmacology and pharmacy

Result continuities

  • 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)

Others

  • Publication year

    2021

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    Bioorganic Chemistry

  • ISSN

    0045-2068

  • e-ISSN

  • Volume of the periodical

    116

  • Issue of the periodical within the volume

    November

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    16

  • Pages from-to

    105301

  • UT code for WoS article

    000701719000006

  • EID of the result in the Scopus database

    2-s2.0-85114160384