SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs
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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2019-01-01
|
| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2019.1593158 |
| _version_ | 1818316794466664448 |
|---|---|
| author | Raed Shalaby Jacobus P. Petzer Anél Petzer Usman M. Ashraf Ealla Atari Fawaz Alasmari Sivarajan Kumarasamy Youssef Sari Ashraf Khalil |
| author_facet | Raed Shalaby Jacobus P. Petzer Anél Petzer Usman M. Ashraf Ealla Atari Fawaz Alasmari Sivarajan Kumarasamy Youssef Sari Ashraf Khalil |
| author_sort | Raed Shalaby |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T09:27:05Z |
| format | Article |
| id | doaj.art-7985cc6fa19d48f0808a64a131e0b1c1 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-13T09:27:05Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-7985cc6fa19d48f0808a64a131e0b1c12022-12-21T23:52:35ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742019-01-0134186387610.1080/14756366.2019.15931581593158SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogsRaed Shalaby0Jacobus P. Petzer1Anél Petzer2Usman M. Ashraf3Ealla Atari4Fawaz Alasmari5Sivarajan Kumarasamy6Youssef Sari7Ashraf Khalil8Qatar UniversityNorth-West UniversityNorth-West UniversityCentre for Hypertension and Personalized Medicine, University of Toledo College of MedicineCentre for Hypertension and Personalized Medicine, University of Toledo College of MedicineCollege of Pharmacy and Pharmaceutical Sciences, The University of ToledoCentre for Hypertension and Personalized Medicine, University of Toledo College of MedicineCollege of Pharmacy and Pharmaceutical Sciences, The University of ToledoQatar UniversityThe 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.http://dx.doi.org/10.1080/14756366.2019.1593158monoamine oxidasechalconereversibilitydopaminemrna |
| spellingShingle | Raed Shalaby Jacobus P. Petzer Anél Petzer Usman M. Ashraf Ealla Atari Fawaz Alasmari Sivarajan Kumarasamy Youssef Sari Ashraf Khalil SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs Journal of Enzyme Inhibition and Medicinal Chemistry monoamine oxidase chalcone reversibility dopamine mrna |
| title | SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs |
| title_full | SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs |
| title_fullStr | SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs |
| title_full_unstemmed | SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs |
| title_short | SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs |
| title_sort | sar and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs |
| topic | monoamine oxidase chalcone reversibility dopamine mrna |
| url | http://dx.doi.org/10.1080/14756366.2019.1593158 |
| work_keys_str_mv | AT raedshalaby sarandmolecularmechanismstudiesofmonoamineoxidaseinhibitionbyselectedchalconeanalogs AT jacobusppetzer sarandmolecularmechanismstudiesofmonoamineoxidaseinhibitionbyselectedchalconeanalogs AT anelpetzer sarandmolecularmechanismstudiesofmonoamineoxidaseinhibitionbyselectedchalconeanalogs AT usmanmashraf sarandmolecularmechanismstudiesofmonoamineoxidaseinhibitionbyselectedchalconeanalogs AT eallaatari sarandmolecularmechanismstudiesofmonoamineoxidaseinhibitionbyselectedchalconeanalogs AT fawazalasmari sarandmolecularmechanismstudiesofmonoamineoxidaseinhibitionbyselectedchalconeanalogs AT sivarajankumarasamy sarandmolecularmechanismstudiesofmonoamineoxidaseinhibitionbyselectedchalconeanalogs AT youssefsari sarandmolecularmechanismstudiesofmonoamineoxidaseinhibitionbyselectedchalconeanalogs AT ashrafkhalil sarandmolecularmechanismstudiesofmonoamineoxidaseinhibitionbyselectedchalconeanalogs |