Discovery of new 6-ureido/amidocoumarins as highly potent and selective inhibitors for the tumour-relevant carbonic anhydrases IX and XII
AbstractA series of 6-ureido/amidocoumarins (5a–p and 7a–c) has been designed and synthesised to develop potent and isoform- selective carbonic anhydrase hCA XI and XII inhibitors. All coumarin derivatives were investigated for their CA inhibitory effect against hCA I, II, IX, and XII. Interestingly...
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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/10.1080/14756366.2022.2154603 |
| _version_ | 1797400949671591936 |
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| author | Ashraf K. El-Damasy Hyun Ji Kim Alessio Nocentini Seon Hee Seo Wagdy M. Eldehna Eun-Kyoung Bang Claudiu T. Supuran Gyochang Keum |
| author_facet | Ashraf K. El-Damasy Hyun Ji Kim Alessio Nocentini Seon Hee Seo Wagdy M. Eldehna Eun-Kyoung Bang Claudiu T. Supuran Gyochang Keum |
| author_sort | Ashraf K. El-Damasy |
| collection | DOAJ |
| description | AbstractA series of 6-ureido/amidocoumarins (5a–p and 7a–c) has been designed and synthesised to develop potent and isoform- selective carbonic anhydrase hCA XI and XII inhibitors. All coumarin derivatives were investigated for their CA inhibitory effect against hCA I, II, IX, and XII. Interestingly, target coumarins potently inhibited both tumour-related isoforms hCA IX (KIs: 14.7–82.4 nM) and hCA XII (KIs: 5.9–95.1 nM), whereas the cytosolic off-target hCA I and II isoforms have not inhibited by all tested coumarins up to 100 μM. These findings granted the target coumarins an excellent selectivity profile towards both hCA IX and hCA XII isoforms, supporting their development as promising anticancer candidates. Moreover, all target molecules were evaluated for their anticancer activities against HCT-116 and MCF-7 cancer cells. The 3,5-bis-trifluoromethylphenyl ureidocoumarin 5i, exerted the best anticancer activity. Overall, ureidocoumarins, particularly compound 5i, could serve as a promising prototype for the development of potent anticancer CAIs. |
| first_indexed | 2024-03-09T02:02:54Z |
| format | Article |
| id | doaj.art-7b6dab7f30fe4aee93cac9edd05477c1 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-09T02:02:54Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-7b6dab7f30fe4aee93cac9edd05477c12023-12-08T03:24:22ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2022.2154603Discovery of new 6-ureido/amidocoumarins as highly potent and selective inhibitors for the tumour-relevant carbonic anhydrases IX and XIIAshraf K. El-Damasy0Hyun Ji Kim1Alessio Nocentini2Seon Hee Seo3Wagdy M. Eldehna4Eun-Kyoung Bang5Claudiu T. Supuran6Gyochang Keum7Center for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South KoreaCenter for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South KoreaSection of Pharmaceutical and Nutraceutical Sciences, Department of NEUROFARBA, University of Florence, Florence, ItalyCenter for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South KoreaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafr El Sheikh, EgyptCenter for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South KoreaSection of Pharmaceutical and Nutraceutical Sciences, Department of NEUROFARBA, University of Florence, Florence, ItalyCenter for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South KoreaAbstractA series of 6-ureido/amidocoumarins (5a–p and 7a–c) has been designed and synthesised to develop potent and isoform- selective carbonic anhydrase hCA XI and XII inhibitors. All coumarin derivatives were investigated for their CA inhibitory effect against hCA I, II, IX, and XII. Interestingly, target coumarins potently inhibited both tumour-related isoforms hCA IX (KIs: 14.7–82.4 nM) and hCA XII (KIs: 5.9–95.1 nM), whereas the cytosolic off-target hCA I and II isoforms have not inhibited by all tested coumarins up to 100 μM. These findings granted the target coumarins an excellent selectivity profile towards both hCA IX and hCA XII isoforms, supporting their development as promising anticancer candidates. Moreover, all target molecules were evaluated for their anticancer activities against HCT-116 and MCF-7 cancer cells. The 3,5-bis-trifluoromethylphenyl ureidocoumarin 5i, exerted the best anticancer activity. Overall, ureidocoumarins, particularly compound 5i, could serve as a promising prototype for the development of potent anticancer CAIs.https://www.tandfonline.com/doi/10.1080/14756366.2022.2154603Ureidocoumarinscarbonic anhydrase IXcarbonic anhydrase XIISLC-0111anticancer activity |
| spellingShingle | Ashraf K. El-Damasy Hyun Ji Kim Alessio Nocentini Seon Hee Seo Wagdy M. Eldehna Eun-Kyoung Bang Claudiu T. Supuran Gyochang Keum Discovery of new 6-ureido/amidocoumarins as highly potent and selective inhibitors for the tumour-relevant carbonic anhydrases IX and XII Journal of Enzyme Inhibition and Medicinal Chemistry Ureidocoumarins carbonic anhydrase IX carbonic anhydrase XII SLC-0111 anticancer activity |
| title | Discovery of new 6-ureido/amidocoumarins as highly potent and selective inhibitors for the tumour-relevant carbonic anhydrases IX and XII |
| title_full | Discovery of new 6-ureido/amidocoumarins as highly potent and selective inhibitors for the tumour-relevant carbonic anhydrases IX and XII |
| title_fullStr | Discovery of new 6-ureido/amidocoumarins as highly potent and selective inhibitors for the tumour-relevant carbonic anhydrases IX and XII |
| title_full_unstemmed | Discovery of new 6-ureido/amidocoumarins as highly potent and selective inhibitors for the tumour-relevant carbonic anhydrases IX and XII |
| title_short | Discovery of new 6-ureido/amidocoumarins as highly potent and selective inhibitors for the tumour-relevant carbonic anhydrases IX and XII |
| title_sort | discovery of new 6 ureido amidocoumarins as highly potent and selective inhibitors for the tumour relevant carbonic anhydrases ix and xii |
| topic | Ureidocoumarins carbonic anhydrase IX carbonic anhydrase XII SLC-0111 anticancer activity |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2154603 |
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