Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine1
The Carbonic Anhydrase (CA, EC 4.2.1.1) activating properties of histamine have been known for a long time. This compound has been extensively modified but only in few instances the imidazole ring has been replaced with other heterocycles. It was envisaged that the imidazoline ring could be a bioiso...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2020.1749602 |
| _version_ | 1818889676516229120 |
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| author | Niccolò Chiaramonte Soumia Maach Caterina Biliotti Andrea Angeli Gianluca Bartolucci Laura Braconi Silvia Dei Elisabetta Teodori Claudiu T. Supuran Maria Novella Romanelli |
| author_facet | Niccolò Chiaramonte Soumia Maach Caterina Biliotti Andrea Angeli Gianluca Bartolucci Laura Braconi Silvia Dei Elisabetta Teodori Claudiu T. Supuran Maria Novella Romanelli |
| author_sort | Niccolò Chiaramonte |
| collection | DOAJ |
| description | The Carbonic Anhydrase (CA, EC 4.2.1.1) activating properties of histamine have been known for a long time. This compound has been extensively modified but only in few instances the imidazole ring has been replaced with other heterocycles. It was envisaged that the imidazoline ring could be a bioisoster of the imidazole moiety. Indeed, we report that clonidine, a 2-aminoimidazoline derivative, was found able to activate several human CA isoforms (hCA I, IV, VA, VII, IX, XII and XIII), with potency in the micromolar range, while it was inactive on hCA II. A series of 2-aminoimidazoline, structurally related to clonidine, was then synthesised and tested on selected hCA isoforms. The compounds were inactive on hCA II while displayed activating properties on hCA I, VA, VII and XIII, with KA values in the micromolar range. Two compounds (10 and 11) showed some preference for the hCA VA or VII isoforms. |
| first_indexed | 2024-12-19T17:12:48Z |
| format | Article |
| id | doaj.art-10709256ba384d548bce6214767605f3 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-19T17:12:48Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-10709256ba384d548bce6214767605f32022-12-21T20:12:58ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742020-01-013511003101010.1080/14756366.2020.17496021749602Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine1Niccolò Chiaramonte0Soumia Maach1Caterina Biliotti2Andrea Angeli3Gianluca Bartolucci4Laura Braconi5Silvia Dei6Elisabetta Teodori7Claudiu T. Supuran8Maria Novella Romanelli9Section of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child’s Health, University of FlorenceSection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child’s Health, University of FlorenceSection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child’s Health, University of FlorenceSection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child’s Health, University of FlorenceSection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child’s Health, University of FlorenceSection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child’s Health, University of FlorenceSection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child’s Health, University of FlorenceSection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child’s Health, University of FlorenceSection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child’s Health, University of FlorenceSection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child’s Health, University of FlorenceThe Carbonic Anhydrase (CA, EC 4.2.1.1) activating properties of histamine have been known for a long time. This compound has been extensively modified but only in few instances the imidazole ring has been replaced with other heterocycles. It was envisaged that the imidazoline ring could be a bioisoster of the imidazole moiety. Indeed, we report that clonidine, a 2-aminoimidazoline derivative, was found able to activate several human CA isoforms (hCA I, IV, VA, VII, IX, XII and XIII), with potency in the micromolar range, while it was inactive on hCA II. A series of 2-aminoimidazoline, structurally related to clonidine, was then synthesised and tested on selected hCA isoforms. The compounds were inactive on hCA II while displayed activating properties on hCA I, VA, VII and XIII, with KA values in the micromolar range. Two compounds (10 and 11) showed some preference for the hCA VA or VII isoforms.http://dx.doi.org/10.1080/14756366.2020.1749602carbonic anhydraseactivatorclonidinehistamineimidazoline |
| spellingShingle | Niccolò Chiaramonte Soumia Maach Caterina Biliotti Andrea Angeli Gianluca Bartolucci Laura Braconi Silvia Dei Elisabetta Teodori Claudiu T. Supuran Maria Novella Romanelli Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine1 Journal of Enzyme Inhibition and Medicinal Chemistry carbonic anhydrase activator clonidine histamine imidazoline |
| title | Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine1 |
| title_full | Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine1 |
| title_fullStr | Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine1 |
| title_full_unstemmed | Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine1 |
| title_short | Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine1 |
| title_sort | synthesis and carbonic anhydrase activating properties of a series of 2 amino imidazolines structurally related to clonidine1 |
| topic | carbonic anhydrase activator clonidine histamine imidazoline |
| url | http://dx.doi.org/10.1080/14756366.2020.1749602 |
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