2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase
In the present study, a series of 2-benzoyl-6-benzylidenecyclohexanone analogs have been synthesized and evaluated for their anti-cholinesterase activity. Among the forty-one analogs, four compounds (38, 39, 40 and 41) have been identified as lead compounds due to their highest inhibition on both AC...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016
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| Online Access: | http://psasir.upm.edu.my/id/eprint/54802/1/2-Benzoyl-6-benzylidenecyclohexanone%20analogs%20as%20potent%20dual%20inhibitors%20of%20acetylcholinesterase%20and%20butyrylcholinesterase.pdf |
| _version_ | 1796976146231853056 |
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| author | Sze, Wei Leong Abas, Faridah Kok, Wai Lam Shaari, Khozirah Lajis, Nordin |
| author_facet | Sze, Wei Leong Abas, Faridah Kok, Wai Lam Shaari, Khozirah Lajis, Nordin |
| author_sort | Sze, Wei Leong |
| collection | UPM |
| description | In the present study, a series of 2-benzoyl-6-benzylidenecyclohexanone analogs have been synthesized and evaluated for their anti-cholinesterase activity. Among the forty-one analogs, four compounds (38, 39, 40 and 41) have been identified as lead compounds due to their highest inhibition on both AChE and BChE activities. Compounds 39 and 40 in particular exhibited highest inhibition on both AChE and BChE with IC50 values of 1.6 μM and 0.6 μM, respectively. Further structure–activity relationship study suggested that presence of a long-chain heterocyclic in one of the rings played a critical role in the dual enzymes’ inhibition. The Lineweaver–Burk plots and docking results suggest that both compounds could simultaneously bind to the PAS and CAS regions of the enzyme. ADMET analysis further confirmed the therapeutic potential of both compounds based upon their high BBB-penetrating. Thus, 2-benzoyl-6-benzylidenecyclohexanone containing long-chain heterocyclic amine analogs represent a new class of cholinesterase inhibitor, which deserve further investigation for their development into therapeutic agents for cognitive diseases such as Alzheimer. |
| first_indexed | 2024-03-06T09:21:36Z |
| format | Article |
| id | upm.eprints-54802 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T09:21:36Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | upm.eprints-548022017-07-06T05:40:32Z http://psasir.upm.edu.my/id/eprint/54802/ 2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase Sze, Wei Leong Abas, Faridah Kok, Wai Lam Shaari, Khozirah Lajis, Nordin In the present study, a series of 2-benzoyl-6-benzylidenecyclohexanone analogs have been synthesized and evaluated for their anti-cholinesterase activity. Among the forty-one analogs, four compounds (38, 39, 40 and 41) have been identified as lead compounds due to their highest inhibition on both AChE and BChE activities. Compounds 39 and 40 in particular exhibited highest inhibition on both AChE and BChE with IC50 values of 1.6 μM and 0.6 μM, respectively. Further structure–activity relationship study suggested that presence of a long-chain heterocyclic in one of the rings played a critical role in the dual enzymes’ inhibition. The Lineweaver–Burk plots and docking results suggest that both compounds could simultaneously bind to the PAS and CAS regions of the enzyme. ADMET analysis further confirmed the therapeutic potential of both compounds based upon their high BBB-penetrating. Thus, 2-benzoyl-6-benzylidenecyclohexanone containing long-chain heterocyclic amine analogs represent a new class of cholinesterase inhibitor, which deserve further investigation for their development into therapeutic agents for cognitive diseases such as Alzheimer. Elsevier 2016 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/54802/1/2-Benzoyl-6-benzylidenecyclohexanone%20analogs%20as%20potent%20dual%20inhibitors%20of%20acetylcholinesterase%20and%20butyrylcholinesterase.pdf Sze, Wei Leong and Abas, Faridah and Kok, Wai Lam and Shaari, Khozirah and Lajis, Nordin (2016) 2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase. Bioorganic & Medicinal Chemistry, 24 (2016). pp. 3742-3751. ISSN 0968-0896; ESSN:1464-3391 10.1016/j.bmc.2016.06.016 |
| spellingShingle | Sze, Wei Leong Abas, Faridah Kok, Wai Lam Shaari, Khozirah Lajis, Nordin 2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase |
| title | 2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase |
| title_full | 2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase |
| title_fullStr | 2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase |
| title_full_unstemmed | 2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase |
| title_short | 2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase |
| title_sort | 2 benzoyl 6 benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase |
| url | http://psasir.upm.edu.my/id/eprint/54802/1/2-Benzoyl-6-benzylidenecyclohexanone%20analogs%20as%20potent%20dual%20inhibitors%20of%20acetylcholinesterase%20and%20butyrylcholinesterase.pdf |
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