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2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase


Citation

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

Abstract

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.


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Additional Metadata

Item Type: Article
Divisions: Faculty of Food Science and Technology
Institute of Bioscience
DOI Number: https://doi.org/10.1016/j.bmc.2016.06.016
Publisher: Elsevier
Keywords: Acetylcholinesterase; Butyrylcholinesterase; 2-Benzoyl-6-benzylidenecyclohexanone; Kinetic studies; Molecular docking
Depositing User: Mohd Hafiz Che Mahasan
Date Deposited: 06 Jul 2017 05:40
Last Modified: 06 Jul 2017 05:40
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1016/j.bmc.2016.06.016
URI: http://psasir.upm.edu.my/id/eprint/54802
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