SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs
<p dir="ltr">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 IC<sub>50</sub> values were found...
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2019
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| _version_ | 1864513552198402048 |
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| author | Raed Shalaby (3756112) |
| author2 | Jacobus P. Petzer (1395751) Anél Petzer (6517940) Usman M. Ashraf (6517943) Ealla Atari (6517946) Fawaz Alasmari (6517949) Sivarajan Kumarasamy (6517952) Youssef Sari (308864) Ashraf Khalil (4591618) |
| author2_role | author author author author author author author author |
| author_facet | Raed Shalaby (3756112) Jacobus P. Petzer (1395751) Anél Petzer (6517940) Usman M. Ashraf (6517943) Ealla Atari (6517946) Fawaz Alasmari (6517949) Sivarajan Kumarasamy (6517952) Youssef Sari (308864) Ashraf Khalil (4591618) |
| author_role | author |
| dc.creator.none.fl_str_mv | Raed Shalaby (3756112) Jacobus P. Petzer (1395751) Anél Petzer (6517940) Usman M. Ashraf (6517943) Ealla Atari (6517946) Fawaz Alasmari (6517949) Sivarajan Kumarasamy (6517952) Youssef Sari (308864) Ashraf Khalil (4591618) |
| dc.date.none.fl_str_mv | 2019-03-27T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1080/14756366.2019.1593158 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/SAR_and_molecular_mechanism_studies_of_monoamine_oxidase_inhibition_by_selected_chalcone_analogs/25347814 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Pharmacology and pharmaceutical sciences Monoamine oxidase chalcone reversibility dopamine mRNA |
| dc.title.none.fl_str_mv | SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">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 IC<sub>50</sub> values were found to be in the micromolar to submicromolar range. The <i>K</i><sub><em>i</em></sub> 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.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Enzyme Inhibition and Medicinal Chemistry<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1080/14756366.2019.1593158" target="_blank">https://dx.doi.org/10.1080/14756366.2019.1593158</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_7c7198f05fbf4b555197206c346f7511 |
| identifier_str_mv | 10.1080/14756366.2019.1593158 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25347814 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogsRaed Shalaby (3756112)Jacobus P. Petzer (1395751)Anél Petzer (6517940)Usman M. Ashraf (6517943)Ealla Atari (6517946)Fawaz Alasmari (6517949)Sivarajan Kumarasamy (6517952)Youssef Sari (308864)Ashraf Khalil (4591618)Biomedical and clinical sciencesPharmacology and pharmaceutical sciencesMonoamine oxidasechalconereversibilitydopaminemRNA<p dir="ltr">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 IC<sub>50</sub> values were found to be in the micromolar to submicromolar range. The <i>K</i><sub><em>i</em></sub> 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.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Enzyme Inhibition and Medicinal Chemistry<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1080/14756366.2019.1593158" target="_blank">https://dx.doi.org/10.1080/14756366.2019.1593158</a></p>2019-03-27T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1080/14756366.2019.1593158https://figshare.com/articles/journal_contribution/SAR_and_molecular_mechanism_studies_of_monoamine_oxidase_inhibition_by_selected_chalcone_analogs/25347814CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/253478142019-03-27T03:00:00Z |
| spellingShingle | SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs Raed Shalaby (3756112) Biomedical and clinical sciences Pharmacology and pharmaceutical sciences Monoamine oxidase chalcone reversibility dopamine mRNA |
| status_str | publishedVersion |
| 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 | Biomedical and clinical sciences Pharmacology and pharmaceutical sciences Monoamine oxidase chalcone reversibility dopamine mRNA |