Analogues of 2 `-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase
A series of C4-substituted tertiary nitrogen-bearing 2 `-hydroxychalcones were designed and synthesised based on a previous mixed type acetylcholinesterase inhibitor. Majority of the 2 `-hydroxychalcone analogues displayed a better inhibition against acetylcholinesterase (AChE) than butyrylcholinest...
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my.um.eprints.342802022-06-13T02:04:38Z http://eprints.um.edu.my/34280/ Analogues of 2 `-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase Sukumaran, Sri Devi Nasir, Shah Bakhtiar Tee, Jia Ti Buckle, Michael J. C. Othman, Rozana Abd Rahman, Noorsaadah Lee, Vannajan Sanghiran Bukhari, Syed Nasir Abbas Chee, Chin Fei QD Chemistry QH301 Biology RM Therapeutics. Pharmacology RS Pharmacy and materia medica A series of C4-substituted tertiary nitrogen-bearing 2 `-hydroxychalcones were designed and synthesised based on a previous mixed type acetylcholinesterase inhibitor. Majority of the 2 `-hydroxychalcone analogues displayed a better inhibition against acetylcholinesterase (AChE) than butyrylcholinesterase (BuChE). Among them, compound 4c was identified as the most potent AChE inhibitor (IC50: 3.3 mu M) and showed the highest selectivity for AChE over BuChE (ratio >30:1). Molecular docking studies suggested that compound 4c interacts with both the peripheral anionic site (PAS) and catalytic anionic site (CAS) regions of AChE. ADMET analysis confirmed the therapeutic potential of compound 4c based on its blood-brain barrier penetrating. Overall, the results suggest that this 2 `-hydroxychalcone deserves further investigation into the therapeutic lead for Alzheimer's disease (AD). Taylor & Francis Ltd 2021-01-01 Article PeerReviewed Sukumaran, Sri Devi and Nasir, Shah Bakhtiar and Tee, Jia Ti and Buckle, Michael J. C. and Othman, Rozana and Abd Rahman, Noorsaadah and Lee, Vannajan Sanghiran and Bukhari, Syed Nasir Abbas and Chee, Chin Fei (2021) Analogues of 2 `-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase. Journal of Enzyme Inhibition and Medicinal Chemistry, 36 (1). pp. 130-137. DOI https://doi.org/10.1080/14756366.2020.1847100 <https://doi.org/10.1080/14756366.2020.1847100>. 10.1080/14756366.2020.1847100 |
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QD Chemistry QH301 Biology RM Therapeutics. Pharmacology RS Pharmacy and materia medica Sukumaran, Sri Devi Nasir, Shah Bakhtiar Tee, Jia Ti Buckle, Michael J. C. Othman, Rozana Abd Rahman, Noorsaadah Lee, Vannajan Sanghiran Bukhari, Syed Nasir Abbas Chee, Chin Fei Analogues of 2 `-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase |
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A series of C4-substituted tertiary nitrogen-bearing 2 `-hydroxychalcones were designed and synthesised based on a previous mixed type acetylcholinesterase inhibitor. Majority of the 2 `-hydroxychalcone analogues displayed a better inhibition against acetylcholinesterase (AChE) than butyrylcholinesterase (BuChE). Among them, compound 4c was identified as the most potent AChE inhibitor (IC50: 3.3 mu M) and showed the highest selectivity for AChE over BuChE (ratio >30:1). Molecular docking studies suggested that compound 4c interacts with both the peripheral anionic site (PAS) and catalytic anionic site (CAS) regions of AChE. ADMET analysis confirmed the therapeutic potential of compound 4c based on its blood-brain barrier penetrating. Overall, the results suggest that this 2 `-hydroxychalcone deserves further investigation into the therapeutic lead for Alzheimer's disease (AD). |
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Article |
author |
Sukumaran, Sri Devi Nasir, Shah Bakhtiar Tee, Jia Ti Buckle, Michael J. C. Othman, Rozana Abd Rahman, Noorsaadah Lee, Vannajan Sanghiran Bukhari, Syed Nasir Abbas Chee, Chin Fei |
author_facet |
Sukumaran, Sri Devi Nasir, Shah Bakhtiar Tee, Jia Ti Buckle, Michael J. C. Othman, Rozana Abd Rahman, Noorsaadah Lee, Vannajan Sanghiran Bukhari, Syed Nasir Abbas Chee, Chin Fei |
author_sort |
Sukumaran, Sri Devi |
title |
Analogues of 2 `-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase |
title_short |
Analogues of 2 `-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase |
title_full |
Analogues of 2 `-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase |
title_fullStr |
Analogues of 2 `-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase |
title_full_unstemmed |
Analogues of 2 `-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase |
title_sort |
analogues of 2 `-hydroxychalcone with modified c4-substituents as the inhibitors against human acetylcholinesterase |
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Taylor & Francis Ltd |
publishDate |
2021 |
url |
http://eprints.um.edu.my/34280/ |
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1735570300036186112 |
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13.18916 |