Manara - Qatar Research Repository
Browse
1/1
3 files

SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs

journal contribution
submitted on 2024-03-06, 10:01 and posted on 2024-03-06, 10:01 authored by Raed Shalaby, Jacobus P. Petzer, Anél Petzer, Usman M. Ashraf, Ealla Atari, Fawaz Alasmari, Sivarajan Kumarasamy, Youssef Sari, Ashraf Khalil

The present study describes the synthesis of a series of 22 chalcone analogs. These compounds were evaluated as potential human MAO-A and MAO-B inhibitors. The compounds showed varied selectivity against the two isoforms. The IC50 values were found to be in the micromolar to submicromolar range. The Ki values of compound 16 were determined to be 0.047 and 0.020 μM for the inhibition of MAO-A and MAO-B, respectively. Dialysis of enzyme-inhibitor mixtures indicated a reversible competitive mode of inhibition. Most of the synthesized chalcone analogs showed a better selectivity toward MAO-B. However, introducing of 2,4,6-trimethoxy substituents on ring B shifted the selectivity toward MAO-A. In addition, we investigated the molecular mechanism of MAO-B inhibition by selected chalcone analogs. Our results revealed that these selected chalcone analogs increased dopamine levels in the rat hepatoma (H4IIE) cells and decreased the relative mRNA expression of the MAO-B enzyme.

Other Information

Published in: Journal of Enzyme Inhibition and Medicinal Chemistry
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.1080/14756366.2019.1593158

Funding

Open Access funding provided by the Qatar National Library.

History

Language

  • English

Publisher

Taylor & Francis

Publication Year

  • 2019

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Qatar University
  • Qatar University Health - QU
  • College of Pharmacy - QU HEALTH

Usage metrics

    Qatar University

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC