New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators
A series of histamine (HST)-related compounds were synthesized and tested for their activating properties on five physiologically relevant human Carbonic Anhydrase (hCA) isoforms (I, II, Va, VII and XIII). The imidazole ring of HST was replaced with different 5-membered heterocycles and the length o...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/2/545 |
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| author | Niccolò Chiaramonte Alessio Gabellini Andrea Angeli Gianluca Bartolucci Laura Braconi Silvia Dei Elisabetta Teodori Claudiu T. Supuran Maria Novella Romanelli |
| author_facet | Niccolò Chiaramonte Alessio Gabellini Andrea Angeli Gianluca Bartolucci Laura Braconi Silvia Dei Elisabetta Teodori Claudiu T. Supuran Maria Novella Romanelli |
| author_sort | Niccolò Chiaramonte |
| collection | DOAJ |
| description | A series of histamine (HST)-related compounds were synthesized and tested for their activating properties on five physiologically relevant human Carbonic Anhydrase (hCA) isoforms (I, II, Va, VII and XIII). The imidazole ring of HST was replaced with different 5-membered heterocycles and the length of the aliphatic chain was varied. For the most interesting compounds some modifications on the terminal amino group were also performed. The most sensitive isoform to activation was hCA I (K<sub>A</sub> values in the low micromolar range), but surprisingly none of the new compounds displayed activity on hCA II. Some derivatives (<b>1</b>, <b>3a</b> and <b>22</b>) displayed an interesting selectivity for activating hCA I over hCA II, Va, VII and XIII. |
| first_indexed | 2024-03-10T00:50:20Z |
| format | Article |
| id | doaj.art-c691e0df158a4c7c9a5f78ef002d8085 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T00:50:20Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c691e0df158a4c7c9a5f78ef002d80852023-11-23T14:53:31ZengMDPI AGMolecules1420-30492022-01-0127254510.3390/molecules27020545New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I ActivatorsNiccolò Chiaramonte0Alessio Gabellini1Andrea Angeli2Gianluca Bartolucci3Laura Braconi4Silvia Dei5Elisabetta Teodori6Claudiu T. Supuran7Maria Novella Romanelli8Section of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Via Ugo Schiff 6, 50019 Florence, ItalySection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Via Ugo Schiff 6, 50019 Florence, ItalySection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Via Ugo Schiff 6, 50019 Florence, ItalySection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Via Ugo Schiff 6, 50019 Florence, ItalySection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Via Ugo Schiff 6, 50019 Florence, ItalySection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Via Ugo Schiff 6, 50019 Florence, ItalySection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Via Ugo Schiff 6, 50019 Florence, ItalySection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Via Ugo Schiff 6, 50019 Florence, ItalySection of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Via Ugo Schiff 6, 50019 Florence, ItalyA series of histamine (HST)-related compounds were synthesized and tested for their activating properties on five physiologically relevant human Carbonic Anhydrase (hCA) isoforms (I, II, Va, VII and XIII). The imidazole ring of HST was replaced with different 5-membered heterocycles and the length of the aliphatic chain was varied. For the most interesting compounds some modifications on the terminal amino group were also performed. The most sensitive isoform to activation was hCA I (K<sub>A</sub> values in the low micromolar range), but surprisingly none of the new compounds displayed activity on hCA II. Some derivatives (<b>1</b>, <b>3a</b> and <b>22</b>) displayed an interesting selectivity for activating hCA I over hCA II, Va, VII and XIII.https://www.mdpi.com/1420-3049/27/2/545carbonic anhydrase activatorsheterocycleshistamine-related compounds |
| spellingShingle | Niccolò Chiaramonte Alessio Gabellini Andrea Angeli Gianluca Bartolucci Laura Braconi Silvia Dei Elisabetta Teodori Claudiu T. Supuran Maria Novella Romanelli New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators Molecules carbonic anhydrase activators heterocycles histamine-related compounds |
| title | New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators |
| title_full | New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators |
| title_fullStr | New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators |
| title_full_unstemmed | New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators |
| title_short | New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators |
| title_sort | new histamine related five membered n heterocycle derivatives as carbonic anhydrase i activators |
| topic | carbonic anhydrase activators heterocycles histamine-related compounds |
| url | https://www.mdpi.com/1420-3049/27/2/545 |
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