Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors
A library of amine, oxime, ether, epoxy and acyl derivatives of the benzobicyclo[3.2.1]octene were synthesized and evaluated as inhibitors of both human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The majority of the tested compounds exhibited higher selectivity for BChE. Structura...
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MDPI AG
2020-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/21/4872 |
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| author | Tena Čadež Ana Grgičević Ramiza Ahmetović Danijela Barić Nikolina Maček Hrvat Zrinka Kovarik Irena Škorić |
| author_facet | Tena Čadež Ana Grgičević Ramiza Ahmetović Danijela Barić Nikolina Maček Hrvat Zrinka Kovarik Irena Škorić |
| author_sort | Tena Čadež |
| collection | DOAJ |
| description | A library of amine, oxime, ether, epoxy and acyl derivatives of the benzobicyclo[3.2.1]octene were synthesized and evaluated as inhibitors of both human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The majority of the tested compounds exhibited higher selectivity for BChE. Structural adjustment for AChE seems to have been achieved by acylation, and the furan ring opening of furo-benzobicyclo[3.2.1]octadiene results for compound <b>51</b> with the highest AChE affinity (IC<sub>50</sub> = 8.3 µM). Interestingly, its analogue, an oxime ether with a benzobicyclo[3.2.1]-skeleton, compound <b>32</b> was one of the most potent BChE inhibitors in this study (IC<sub>50</sub> = 31 µM), but not as potent as <i>endo-</i><b>43</b>, an ether derivative of the benzobicyclo[3.2.1]octene with an additional phenyl substituent (IC<sub>50</sub> = 17 µM). Therefore, we identified several cholinesterase inhibitors with a potential for further development as potential drugs for the treatment of neurodegenerative diseases. |
| first_indexed | 2024-03-10T15:25:50Z |
| format | Article |
| id | doaj.art-a0512826e8954e59a659d69e27e9d66c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:25:50Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a0512826e8954e59a659d69e27e9d66c2023-11-20T18:04:04ZengMDPI AGMolecules1420-30492020-10-012521487210.3390/molecules25214872Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase InhibitorsTena Čadež0Ana Grgičević1Ramiza Ahmetović2Danijela Barić3Nikolina Maček Hrvat4Zrinka Kovarik5Irena Škorić6Institute for Medical Research and Occupational Health, Ksaverska Cesta 2, 10000 Zagreb, CroatiaDepartment of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, 10000 Zagreb, CroatiaDepartment of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, 10000 Zagreb, CroatiaDivision of Physical Chemistry, Rudjer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, CroatiaInstitute for Medical Research and Occupational Health, Ksaverska Cesta 2, 10000 Zagreb, CroatiaInstitute for Medical Research and Occupational Health, Ksaverska Cesta 2, 10000 Zagreb, CroatiaDepartment of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, 10000 Zagreb, CroatiaA library of amine, oxime, ether, epoxy and acyl derivatives of the benzobicyclo[3.2.1]octene were synthesized and evaluated as inhibitors of both human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The majority of the tested compounds exhibited higher selectivity for BChE. Structural adjustment for AChE seems to have been achieved by acylation, and the furan ring opening of furo-benzobicyclo[3.2.1]octadiene results for compound <b>51</b> with the highest AChE affinity (IC<sub>50</sub> = 8.3 µM). Interestingly, its analogue, an oxime ether with a benzobicyclo[3.2.1]-skeleton, compound <b>32</b> was one of the most potent BChE inhibitors in this study (IC<sub>50</sub> = 31 µM), but not as potent as <i>endo-</i><b>43</b>, an ether derivative of the benzobicyclo[3.2.1]octene with an additional phenyl substituent (IC<sub>50</sub> = 17 µM). Therefore, we identified several cholinesterase inhibitors with a potential for further development as potential drugs for the treatment of neurodegenerative diseases.https://www.mdpi.com/1420-3049/25/21/4872acylationbenzobicyclo[3.2.1]octane/octenebenzylaminescholinesteraseepoxidationoximes |
| spellingShingle | Tena Čadež Ana Grgičević Ramiza Ahmetović Danijela Barić Nikolina Maček Hrvat Zrinka Kovarik Irena Škorić Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors Molecules acylation benzobicyclo[3.2.1]octane/octene benzylamines cholinesterase epoxidation oximes |
| title | Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors |
| title_full | Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors |
| title_fullStr | Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors |
| title_full_unstemmed | Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors |
| title_short | Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors |
| title_sort | benzobicyclo 3 2 1 octene derivatives as a new class of cholinesterase inhibitors |
| topic | acylation benzobicyclo[3.2.1]octane/octene benzylamines cholinesterase epoxidation oximes |
| url | https://www.mdpi.com/1420-3049/25/21/4872 |
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