Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors
Monoamine oxidase (MAO) isoenzymes are very important drug targets among neurological disorders. Herein, novel series of thiazolylhydrazine-piperazine derivatives were designed, synthesized and evaluated for their MAO-A and -B inhibitory activity. The structures of the synthesized compounds were ass...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/18/4342 |
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| author | Begüm Nurpelin Sağlık Osman Cebeci Ulviye Acar Çevik Derya Osmaniye Serkan Levent Betül Kaya Çavuşoğlu Sinem Ilgın Yusuf Özkay Zafer Asım Kaplancıklı |
| author_facet | Begüm Nurpelin Sağlık Osman Cebeci Ulviye Acar Çevik Derya Osmaniye Serkan Levent Betül Kaya Çavuşoğlu Sinem Ilgın Yusuf Özkay Zafer Asım Kaplancıklı |
| author_sort | Begüm Nurpelin Sağlık |
| collection | DOAJ |
| description | Monoamine oxidase (MAO) isoenzymes are very important drug targets among neurological disorders. Herein, novel series of thiazolylhydrazine-piperazine derivatives were designed, synthesized and evaluated for their MAO-A and -B inhibitory activity. The structures of the synthesized compounds were assigned using different spectroscopic techniques such as <sup>1</sup>H-NMR, <sup>13</sup>C-NMR and HRMS. Moreover, the prediction of ADME (Absorption, Distribution, Metabolism, Elimination) parameters for all of the compounds were performed using in silico method. According to the enzyme inhibition results, the synthesized compounds showed the selectivity against MAO-A enzyme inhibition. Compounds <b>3c</b>, <b>3d</b> and <b>3e</b> displayed significant MAO-A inhibition potencies. Among them, compound <b>3e</b> was found to be the most effective derivative with an IC<sub>50</sub> value of 0.057 ± 0.002 µM. Moreover, it was seen that this compound has a more potent inhibition profile than the reference inhibitors moclobemide (IC<sub>50</sub> = 6.061 ± 0.262 µM) and clorgiline (IC<sub>50</sub> = 0.062 ± 0.002 µM). In addition, the enzyme kinetics were performed for compound <b>3e</b> and it was determined that this compound had a competitive and reversible inhibition type. Molecular modeling studies aided in the understanding of the interaction modes between this compound and MAO-A. It was found that compound 3e had significant and important binding property. |
| first_indexed | 2024-03-10T16:08:36Z |
| format | Article |
| id | doaj.art-4d77e513dadf41a8933679f0bae16c46 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T16:08:36Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4d77e513dadf41a8933679f0bae16c462023-11-20T14:39:14ZengMDPI AGMolecules1420-30492020-09-012518434210.3390/molecules25184342Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A InhibitorsBegüm Nurpelin Sağlık0Osman Cebeci1Ulviye Acar Çevik2Derya Osmaniye3Serkan Levent4Betül Kaya Çavuşoğlu5Sinem Ilgın6Yusuf Özkay7Zafer Asım Kaplancıklı8Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Zonguldak Bülent Ecevit University, Zonguldak 67600, TurkeyDepartment of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyMonoamine oxidase (MAO) isoenzymes are very important drug targets among neurological disorders. Herein, novel series of thiazolylhydrazine-piperazine derivatives were designed, synthesized and evaluated for their MAO-A and -B inhibitory activity. The structures of the synthesized compounds were assigned using different spectroscopic techniques such as <sup>1</sup>H-NMR, <sup>13</sup>C-NMR and HRMS. Moreover, the prediction of ADME (Absorption, Distribution, Metabolism, Elimination) parameters for all of the compounds were performed using in silico method. According to the enzyme inhibition results, the synthesized compounds showed the selectivity against MAO-A enzyme inhibition. Compounds <b>3c</b>, <b>3d</b> and <b>3e</b> displayed significant MAO-A inhibition potencies. Among them, compound <b>3e</b> was found to be the most effective derivative with an IC<sub>50</sub> value of 0.057 ± 0.002 µM. Moreover, it was seen that this compound has a more potent inhibition profile than the reference inhibitors moclobemide (IC<sub>50</sub> = 6.061 ± 0.262 µM) and clorgiline (IC<sub>50</sub> = 0.062 ± 0.002 µM). In addition, the enzyme kinetics were performed for compound <b>3e</b> and it was determined that this compound had a competitive and reversible inhibition type. Molecular modeling studies aided in the understanding of the interaction modes between this compound and MAO-A. It was found that compound 3e had significant and important binding property.https://www.mdpi.com/1420-3049/25/18/4342ADME propertiesin vitro enzyme inhibitionmolecular dockingmonoamine oxidasesthiazolylhydrazinepiperazine |
| spellingShingle | Begüm Nurpelin Sağlık Osman Cebeci Ulviye Acar Çevik Derya Osmaniye Serkan Levent Betül Kaya Çavuşoğlu Sinem Ilgın Yusuf Özkay Zafer Asım Kaplancıklı Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors Molecules ADME properties in vitro enzyme inhibition molecular docking monoamine oxidases thiazolylhydrazine piperazine |
| title | Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors |
| title_full | Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors |
| title_fullStr | Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors |
| title_full_unstemmed | Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors |
| title_short | Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors |
| title_sort | design synthesis in vitro and in silico studies of new thiazolylhydrazine piperazine derivatives as selective mao a inhibitors |
| topic | ADME properties in vitro enzyme inhibition molecular docking monoamine oxidases thiazolylhydrazine piperazine |
| url | https://www.mdpi.com/1420-3049/25/18/4342 |
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