Carbonic anhydrase inhibitory activity of phthalimide-capped benzene sulphonamide derivatives
AbstractA series of phthalimide-capped benzene sulphonamides (1–22) reported by our group for dengue protease inhibitory activity have been evaluated for their carbonic anhydrase (hCA, EC 4.2.1.1) inhibitory activity against hCA I, hCA II. Compounds 1, 3, 10, and 15 showed hCA I inhibition, whereas...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2235089 |
| _version_ | 1797400938024009728 |
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| author | Deepak Shilkar Mohd Usman Mohd Siddique Silvia Bua Sabina Yasmin Mrunali Patil Ajay Kumar Timiri Claudiu T. Supuran Venkatesan Jayaprakash |
| author_facet | Deepak Shilkar Mohd Usman Mohd Siddique Silvia Bua Sabina Yasmin Mrunali Patil Ajay Kumar Timiri Claudiu T. Supuran Venkatesan Jayaprakash |
| author_sort | Deepak Shilkar |
| collection | DOAJ |
| description | AbstractA series of phthalimide-capped benzene sulphonamides (1–22) reported by our group for dengue protease inhibitory activity have been evaluated for their carbonic anhydrase (hCA, EC 4.2.1.1) inhibitory activity against hCA I, hCA II. Compounds 1, 3, 10, and 15 showed hCA I inhibition, whereas 1, 4, and 10 showed hCA II inhibition at nanomolar concentrations. Among these compounds, 1 displayed potent inhibitory activity against the hCA I (Ki = 28.5 nM) and hCA II (Ki = 2.2 nM), being 10 and 6 times more potent than acetazolamide, a standard inhibitor (Ki = 250 nM and 12 nM), respectively. Furthermore, this compound displayed 14-fold selectivity towards the hCA II isoform compared to hCA I. Molecular docking and MD simulations were performed to understand the atomic level interactions responsible for the selectivity of compound 1 towards hCA II. |
| first_indexed | 2024-03-09T02:02:43Z |
| format | Article |
| id | doaj.art-4bbdbcfd8fd24e2fbfa0939436c3abe1 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-09T02:02:43Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-4bbdbcfd8fd24e2fbfa0939436c3abe12023-12-08T03:24:20ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2235089Carbonic anhydrase inhibitory activity of phthalimide-capped benzene sulphonamide derivativesDeepak Shilkar0Mohd Usman Mohd Siddique1Silvia Bua2Sabina Yasmin3Mrunali Patil4Ajay Kumar Timiri5Claudiu T. Supuran6Venkatesan Jayaprakash7Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Ranchi, IndiaDepartment of Pharmaceutical Chemistry, Shri Vile Parle Kelavani Mandal’s Institute of Pharmacy, Dhule, IndiaNeurofarba Department, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Firenze, ItalyDepartment of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Ranchi, IndiaDepartment of Pharmaceutical Chemistry, Shri Vile Parle Kelavani Mandal’s Institute of Pharmacy, Dhule, IndiaDepartment of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Ranchi, IndiaNeurofarba Department, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Firenze, ItalyDepartment of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Ranchi, IndiaAbstractA series of phthalimide-capped benzene sulphonamides (1–22) reported by our group for dengue protease inhibitory activity have been evaluated for their carbonic anhydrase (hCA, EC 4.2.1.1) inhibitory activity against hCA I, hCA II. Compounds 1, 3, 10, and 15 showed hCA I inhibition, whereas 1, 4, and 10 showed hCA II inhibition at nanomolar concentrations. Among these compounds, 1 displayed potent inhibitory activity against the hCA I (Ki = 28.5 nM) and hCA II (Ki = 2.2 nM), being 10 and 6 times more potent than acetazolamide, a standard inhibitor (Ki = 250 nM and 12 nM), respectively. Furthermore, this compound displayed 14-fold selectivity towards the hCA II isoform compared to hCA I. Molecular docking and MD simulations were performed to understand the atomic level interactions responsible for the selectivity of compound 1 towards hCA II.https://www.tandfonline.com/doi/10.1080/14756366.2023.2235089Carbonic anhydrasephthalyl sulphamoyl derivativesmolecular dockingmolecular dynamics |
| spellingShingle | Deepak Shilkar Mohd Usman Mohd Siddique Silvia Bua Sabina Yasmin Mrunali Patil Ajay Kumar Timiri Claudiu T. Supuran Venkatesan Jayaprakash Carbonic anhydrase inhibitory activity of phthalimide-capped benzene sulphonamide derivatives Journal of Enzyme Inhibition and Medicinal Chemistry Carbonic anhydrase phthalyl sulphamoyl derivatives molecular docking molecular dynamics |
| title | Carbonic anhydrase inhibitory activity of phthalimide-capped benzene sulphonamide derivatives |
| title_full | Carbonic anhydrase inhibitory activity of phthalimide-capped benzene sulphonamide derivatives |
| title_fullStr | Carbonic anhydrase inhibitory activity of phthalimide-capped benzene sulphonamide derivatives |
| title_full_unstemmed | Carbonic anhydrase inhibitory activity of phthalimide-capped benzene sulphonamide derivatives |
| title_short | Carbonic anhydrase inhibitory activity of phthalimide-capped benzene sulphonamide derivatives |
| title_sort | carbonic anhydrase inhibitory activity of phthalimide capped benzene sulphonamide derivatives |
| topic | Carbonic anhydrase phthalyl sulphamoyl derivatives molecular docking molecular dynamics |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2235089 |
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