Evaluation of N-alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitors
AbstractTwo series of N-alkyl isatins and N-alkyl indoles varying in size of the alkyl group were synthesised and evaluated for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the N-alkyl isatins 4a-j, the addition of the N-alkyl group improved inhibition potency to...
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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 |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2286935 |
| _version_ | 1797401571381739520 |
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| author | Kaitlyn N. Alcorn Isabelle A. Oberhauser Matthew D. Politeski Todd J. Eckroat |
| author_facet | Kaitlyn N. Alcorn Isabelle A. Oberhauser Matthew D. Politeski Todd J. Eckroat |
| author_sort | Kaitlyn N. Alcorn |
| collection | DOAJ |
| description | AbstractTwo series of N-alkyl isatins and N-alkyl indoles varying in size of the alkyl group were synthesised and evaluated for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the N-alkyl isatins 4a-j, the addition of the N-alkyl group improved inhibition potency towards AChE and BChE compared to isatin. Selectivity towards inhibition of BChE was observed, and the increase in size of the N-alkyl group positively correlated to improved inhibition potency. The most potent inhibitor for BChE was 4i (IC50 = 3.77 µM, 22-fold selectivity for BChE over AChE). N-alkyl indoles 5a-j showed similar inhibition of AChE, the most potent being 5g (IC50 = 35.0 µM), but 5a-j lost activity towards BChE. This suggests an important role of the 3-oxo group on isatin for BChE inhibition, and molecular docking of 4i with human BChE indicates a key hydrogen bond between this group and Ser198 and His438 of the BChE catalytic triad. |
| first_indexed | 2024-03-09T02:12:01Z |
| format | Article |
| id | doaj.art-baa31d7bccf24974a1047f6ad747a388 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-09T02:12:01Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-baa31d7bccf24974a1047f6ad747a3882023-12-07T08:48:09ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2023.2286935Evaluation of N-alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitorsKaitlyn N. Alcorn0Isabelle A. Oberhauser1Matthew D. Politeski2Todd J. Eckroat3School of Science, Penn State Erie, The Behrend College, Erie, PA, USASchool of Science, Penn State Erie, The Behrend College, Erie, PA, USASchool of Science, Penn State Erie, The Behrend College, Erie, PA, USASchool of Science, Penn State Erie, The Behrend College, Erie, PA, USAAbstractTwo series of N-alkyl isatins and N-alkyl indoles varying in size of the alkyl group were synthesised and evaluated for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the N-alkyl isatins 4a-j, the addition of the N-alkyl group improved inhibition potency towards AChE and BChE compared to isatin. Selectivity towards inhibition of BChE was observed, and the increase in size of the N-alkyl group positively correlated to improved inhibition potency. The most potent inhibitor for BChE was 4i (IC50 = 3.77 µM, 22-fold selectivity for BChE over AChE). N-alkyl indoles 5a-j showed similar inhibition of AChE, the most potent being 5g (IC50 = 35.0 µM), but 5a-j lost activity towards BChE. This suggests an important role of the 3-oxo group on isatin for BChE inhibition, and molecular docking of 4i with human BChE indicates a key hydrogen bond between this group and Ser198 and His438 of the BChE catalytic triad.https://www.tandfonline.com/doi/10.1080/14756366.2023.2286935Isatinindoleacetylcholinesterasebutyrylcholinesterase |
| spellingShingle | Kaitlyn N. Alcorn Isabelle A. Oberhauser Matthew D. Politeski Todd J. Eckroat Evaluation of N-alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry Isatin indole acetylcholinesterase butyrylcholinesterase |
| title | Evaluation of N-alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitors |
| title_full | Evaluation of N-alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitors |
| title_fullStr | Evaluation of N-alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitors |
| title_full_unstemmed | Evaluation of N-alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitors |
| title_short | Evaluation of N-alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitors |
| title_sort | evaluation of n alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitors |
| topic | Isatin indole acetylcholinesterase butyrylcholinesterase |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2286935 |
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