Synthesis, Biological Evaluation and Molecular Modelling of 2′-Hydroxychalcones as Acetylcholinesterase Inhibitors
A series of 2′-hydroxy- and 2′-hydroxy-4′,6′-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE). The majority of the compounds were found to show some activity, with the most active compounds having IC50 values of 40–85 µM. Higher activities were gene...
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MDPI AG
2016-07-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/7/955 |
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doaj-311afe94396f4104981b3e3f12226bab2020-11-24T23:13:55ZengMDPI AGMolecules1420-30492016-07-0121795510.3390/molecules21070955molecules21070955Synthesis, Biological Evaluation and Molecular Modelling of 2′-Hydroxychalcones as Acetylcholinesterase InhibitorsSri Devi Sukumaran0Chin Fei Chee1Geetha Viswanathan2Michael J. C. Buckle3Rozana Othman4Noorsaadah Abd. Rahman5Lip Yong Chung6Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaDepartment of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaDepartment of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaDepartment of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaDepartment of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaDepartment of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, MalaysiaDepartment of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaA series of 2′-hydroxy- and 2′-hydroxy-4′,6′-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE). The majority of the compounds were found to show some activity, with the most active compounds having IC50 values of 40–85 µM. Higher activities were generally observed for compounds with methoxy substituents in the A ring and halogen substituents in the B ring. Kinetic studies on the most active compounds showed that they act as mixed-type inhibitors, in agreement with the results of molecular modelling studies, which suggested that they interact with residues in the peripheral anionic site and the gorge region of AChE.http://www.mdpi.com/1420-3049/21/7/955Alzheimer’s diseaseacetylcholinesterasechalconesmolecular modelling |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Sri Devi Sukumaran Chin Fei Chee Geetha Viswanathan Michael J. C. Buckle Rozana Othman Noorsaadah Abd. Rahman Lip Yong Chung |
| spellingShingle |
Sri Devi Sukumaran Chin Fei Chee Geetha Viswanathan Michael J. C. Buckle Rozana Othman Noorsaadah Abd. Rahman Lip Yong Chung Synthesis, Biological Evaluation and Molecular Modelling of 2′-Hydroxychalcones as Acetylcholinesterase Inhibitors Molecules Alzheimer’s disease acetylcholinesterase chalcones molecular modelling |
| author_facet |
Sri Devi Sukumaran Chin Fei Chee Geetha Viswanathan Michael J. C. Buckle Rozana Othman Noorsaadah Abd. Rahman Lip Yong Chung |
| author_sort |
Sri Devi Sukumaran |
| title |
Synthesis, Biological Evaluation and Molecular Modelling of 2′-Hydroxychalcones as Acetylcholinesterase Inhibitors |
| title_short |
Synthesis, Biological Evaluation and Molecular Modelling of 2′-Hydroxychalcones as Acetylcholinesterase Inhibitors |
| title_full |
Synthesis, Biological Evaluation and Molecular Modelling of 2′-Hydroxychalcones as Acetylcholinesterase Inhibitors |
| title_fullStr |
Synthesis, Biological Evaluation and Molecular Modelling of 2′-Hydroxychalcones as Acetylcholinesterase Inhibitors |
| title_full_unstemmed |
Synthesis, Biological Evaluation and Molecular Modelling of 2′-Hydroxychalcones as Acetylcholinesterase Inhibitors |
| title_sort |
synthesis, biological evaluation and molecular modelling of 2′-hydroxychalcones as acetylcholinesterase inhibitors |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2016-07-01 |
| description |
A series of 2′-hydroxy- and 2′-hydroxy-4′,6′-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE). The majority of the compounds were found to show some activity, with the most active compounds having IC50 values of 40–85 µM. Higher activities were generally observed for compounds with methoxy substituents in the A ring and halogen substituents in the B ring. Kinetic studies on the most active compounds showed that they act as mixed-type inhibitors, in agreement with the results of molecular modelling studies, which suggested that they interact with residues in the peripheral anionic site and the gorge region of AChE. |
| topic |
Alzheimer’s disease acetylcholinesterase chalcones molecular modelling |
| url |
http://www.mdpi.com/1420-3049/21/7/955 |
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