Synthesis, carbonic anhydrase inhibition studies and modelling investigations of phthalimide–hydantoin hybrids
A novel series of hydantoins incorporating phthalimides has been synthesised by condensation of activated phthalimides with 1-aminohydantoin and investigated for their inhibitory activity against a panel of human (h) carbonic anhydrase (CA, EC 4.2.1.1): the cytosolic isoforms hCA I, hCA II, and hCA...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2024.2335927 |
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| author | Morteza Abdoli Alessandro Bonardi Paola Gratteri Claudiu T. Supuran Raivis Žalubovskis |
| author_facet | Morteza Abdoli Alessandro Bonardi Paola Gratteri Claudiu T. Supuran Raivis Žalubovskis |
| author_sort | Morteza Abdoli |
| collection | DOAJ |
| description | A novel series of hydantoins incorporating phthalimides has been synthesised by condensation of activated phthalimides with 1-aminohydantoin and investigated for their inhibitory activity against a panel of human (h) carbonic anhydrase (CA, EC 4.2.1.1): the cytosolic isoforms hCA I, hCA II, and hCA VII, secreted isoform hCA VI, and the transmembrane hCA IX, by a stopped-flow CO2 hydrase assay. Although all newly developed compounds were totally inactive on hCA I and mainly ineffective towards hCA II, they generally exhibited moderate repressing effects on hCA VI, VII, and IX with KIs values in the submicromolar to micromolar ranges. The salts 3a and 3b, followed by derivative 5, displayed the best inhibitory activity of all the evaluated compounds and their binding mode was proposed in silico. These compounds can also be considered interesting starting points for the development of novel pharmacophores for this class of enzyme inhibitors. |
| format | Article |
| id | doaj-art-e4dede48e0c541abb1dbd975df0400c2 |
| institution | DOAJ |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-e4dede48e0c541abb1dbd975df0400c22025-08-20T02:40:34ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2024.2335927Synthesis, carbonic anhydrase inhibition studies and modelling investigations of phthalimide–hydantoin hybridsMorteza Abdoli0Alessandro Bonardi1Paola Gratteri2Claudiu T. Supuran3Raivis Žalubovskis4Institute of Chemistry and Chemical Technology, Faculty of Natural Sciences and Technology, Riga Technical University, Riga, LatviaDepartment NEUROFARBA – Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Sesto Fiorentino (Florence), ItalyDepartment NEUROFARBA – Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Sesto Fiorentino (Florence), ItalyDepartment of NEUROFARBA – Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Sesto Fiorentino (Florence), ItalyInstitute of Chemistry and Chemical Technology, Faculty of Natural Sciences and Technology, Riga Technical University, Riga, LatviaA novel series of hydantoins incorporating phthalimides has been synthesised by condensation of activated phthalimides with 1-aminohydantoin and investigated for their inhibitory activity against a panel of human (h) carbonic anhydrase (CA, EC 4.2.1.1): the cytosolic isoforms hCA I, hCA II, and hCA VII, secreted isoform hCA VI, and the transmembrane hCA IX, by a stopped-flow CO2 hydrase assay. Although all newly developed compounds were totally inactive on hCA I and mainly ineffective towards hCA II, they generally exhibited moderate repressing effects on hCA VI, VII, and IX with KIs values in the submicromolar to micromolar ranges. The salts 3a and 3b, followed by derivative 5, displayed the best inhibitory activity of all the evaluated compounds and their binding mode was proposed in silico. These compounds can also be considered interesting starting points for the development of novel pharmacophores for this class of enzyme inhibitors.https://www.tandfonline.com/doi/10.1080/14756366.2024.2335927Carbonic anhydraseinhibitorshydantoinsphthalimidesdocking studies |
| spellingShingle | Morteza Abdoli Alessandro Bonardi Paola Gratteri Claudiu T. Supuran Raivis Žalubovskis Synthesis, carbonic anhydrase inhibition studies and modelling investigations of phthalimide–hydantoin hybrids Journal of Enzyme Inhibition and Medicinal Chemistry Carbonic anhydrase inhibitors hydantoins phthalimides docking studies |
| title | Synthesis, carbonic anhydrase inhibition studies and modelling investigations of phthalimide–hydantoin hybrids |
| title_full | Synthesis, carbonic anhydrase inhibition studies and modelling investigations of phthalimide–hydantoin hybrids |
| title_fullStr | Synthesis, carbonic anhydrase inhibition studies and modelling investigations of phthalimide–hydantoin hybrids |
| title_full_unstemmed | Synthesis, carbonic anhydrase inhibition studies and modelling investigations of phthalimide–hydantoin hybrids |
| title_short | Synthesis, carbonic anhydrase inhibition studies and modelling investigations of phthalimide–hydantoin hybrids |
| title_sort | synthesis carbonic anhydrase inhibition studies and modelling investigations of phthalimide hydantoin hybrids |
| topic | Carbonic anhydrase inhibitors hydantoins phthalimides docking studies |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2024.2335927 |
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