Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes
The present study aimed to develop potent carbonic anhydrase inhibitors (CAIs). The design of the target compounds was based on modifying the structure of the ureido-based carbonic anhydrase inhibitor SLC-0111. Six series of a substituted benzoylthioureido core were prepared featuring different zinc...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
|
| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2126463 |
| _version_ | 1811206259124207616 |
|---|---|
| author | Mazin A. A. Najm Walaa R. Mahmoud Azza T. Taher Safinaz E-S. Abbas Fadi M. Awadallah Heba Abdelrasheed Allam Daniela Vullo Claudiu T. Supuran |
| author_facet | Mazin A. A. Najm Walaa R. Mahmoud Azza T. Taher Safinaz E-S. Abbas Fadi M. Awadallah Heba Abdelrasheed Allam Daniela Vullo Claudiu T. Supuran |
| author_sort | Mazin A. A. Najm |
| collection | DOAJ |
| description | The present study aimed to develop potent carbonic anhydrase inhibitors (CAIs). The design of the target compounds was based on modifying the structure of the ureido-based carbonic anhydrase inhibitor SLC-0111. Six series of a substituted benzoylthioureido core were prepared featuring different zinc-binding groups; the conventional sulphamoyl group 4a–d and 12a–c, its bioisosteric carboxylic acid group 5a–d and 13a–c or the ethyl carboxylate group 6a–d and 14a–c as potential prodrugs. All compounds were assessed for their carbonic anhydrase (CA) inhibitory activity against a panel of four physiologically relevant human CA isoforms hCA I and hCA II, and hCA IX, and hCA XII. Compounds 4a, 4b, 4c, 4d, 5d, 12a, and 12c revealed significant inhibitory activity against hCA I that would highlight these compounds as promising drug candidates for the treatment of glaucoma. |
| first_indexed | 2024-04-12T03:45:30Z |
| format | Article |
| id | doaj.art-c435c9c5839048bfb876e8744a19fddd |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-12T03:45:30Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-c435c9c5839048bfb876e8744a19fddd2022-12-22T03:49:10ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013712702270910.1080/14756366.2022.2126463Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymesMazin A. A. Najm0Walaa R. Mahmoud1Azza T. Taher2Safinaz E-S. Abbas3Fadi M. Awadallah4Heba Abdelrasheed Allam5Daniela Vullo6Claudiu T. Supuran7Department of Pharmaceutical Chemistry, College of Pharmacy, Al-Ayen University, Thi-Qar, IraqDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, EgyptDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, EgyptDepartment of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Firenze, ItalyDepartment of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Firenze, ItalyThe present study aimed to develop potent carbonic anhydrase inhibitors (CAIs). The design of the target compounds was based on modifying the structure of the ureido-based carbonic anhydrase inhibitor SLC-0111. Six series of a substituted benzoylthioureido core were prepared featuring different zinc-binding groups; the conventional sulphamoyl group 4a–d and 12a–c, its bioisosteric carboxylic acid group 5a–d and 13a–c or the ethyl carboxylate group 6a–d and 14a–c as potential prodrugs. All compounds were assessed for their carbonic anhydrase (CA) inhibitory activity against a panel of four physiologically relevant human CA isoforms hCA I and hCA II, and hCA IX, and hCA XII. Compounds 4a, 4b, 4c, 4d, 5d, 12a, and 12c revealed significant inhibitory activity against hCA I that would highlight these compounds as promising drug candidates for the treatment of glaucoma.https://www.tandfonline.com/doi/10.1080/14756366.2022.2126463Sulphonamidescarbonic anhydraseSLC-0111benzoylthioureido derivatives |
| spellingShingle | Mazin A. A. Najm Walaa R. Mahmoud Azza T. Taher Safinaz E-S. Abbas Fadi M. Awadallah Heba Abdelrasheed Allam Daniela Vullo Claudiu T. Supuran Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes Journal of Enzyme Inhibition and Medicinal Chemistry Sulphonamides carbonic anhydrase SLC-0111 benzoylthioureido derivatives |
| title | Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes |
| title_full | Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes |
| title_fullStr | Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes |
| title_full_unstemmed | Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes |
| title_short | Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes |
| title_sort | design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes |
| topic | Sulphonamides carbonic anhydrase SLC-0111 benzoylthioureido derivatives |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2126463 |
| work_keys_str_mv | AT mazinaanajm designandsynthesisofsomenewbenzoylthioureidophenylderivativestargetingcarbonicanhydraseenzymes AT walaarmahmoud designandsynthesisofsomenewbenzoylthioureidophenylderivativestargetingcarbonicanhydraseenzymes AT azzattaher designandsynthesisofsomenewbenzoylthioureidophenylderivativestargetingcarbonicanhydraseenzymes AT safinazesabbas designandsynthesisofsomenewbenzoylthioureidophenylderivativestargetingcarbonicanhydraseenzymes AT fadimawadallah designandsynthesisofsomenewbenzoylthioureidophenylderivativestargetingcarbonicanhydraseenzymes AT hebaabdelrasheedallam designandsynthesisofsomenewbenzoylthioureidophenylderivativestargetingcarbonicanhydraseenzymes AT danielavullo designandsynthesisofsomenewbenzoylthioureidophenylderivativestargetingcarbonicanhydraseenzymes AT claudiutsupuran designandsynthesisofsomenewbenzoylthioureidophenylderivativestargetingcarbonicanhydraseenzymes |