2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones as inhibitors of cholinesterases and self-induced β-amyloid (Aβ) aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations
A series of 2-aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones were evaluated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and self-induced β-amyloid (Aβ) aggregation. All the compounds were found to inhibit both forms of cholinesterase (IC50 in the range 4-32...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Published: |
Royal Society of Chemistry
2018
|
| Subjects: |
| _version_ | 1825721530404831232 |
|---|---|
| author | Sukumaran, Sri Devi Faraj, Fadhil Lafta Lee, Vannajan Sanghiran Othman, Rozana Buckle, Michael James Christopher |
| author_facet | Sukumaran, Sri Devi Faraj, Fadhil Lafta Lee, Vannajan Sanghiran Othman, Rozana Buckle, Michael James Christopher |
| author_sort | Sukumaran, Sri Devi |
| collection | UM |
| description | A series of 2-aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones were evaluated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and self-induced β-amyloid (Aβ) aggregation. All the compounds were found to inhibit both forms of cholinesterase (IC50 in the range 4-32 μM) with some selectivity for BuChE. Most of the compounds also showed self-induced Aβ aggregation inhibitory activities, which were comparable or higher than those obtained for reference compounds, curcumin and myricetin. Docking and molecular dynamics (MD) simulation experiments suggested that the compounds are able to disrupt the dimer form of Aβ. |
| first_indexed | 2024-03-06T05:51:41Z |
| format | Article |
| id | um.eprints-20600 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T05:51:41Z |
| publishDate | 2018 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | um.eprints-206002019-03-05T02:11:19Z http://eprints.um.edu.my/20600/ 2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones as inhibitors of cholinesterases and self-induced β-amyloid (Aβ) aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations Sukumaran, Sri Devi Faraj, Fadhil Lafta Lee, Vannajan Sanghiran Othman, Rozana Buckle, Michael James Christopher Q Science (General) QD Chemistry R Medicine A series of 2-aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones were evaluated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and self-induced β-amyloid (Aβ) aggregation. All the compounds were found to inhibit both forms of cholinesterase (IC50 in the range 4-32 μM) with some selectivity for BuChE. Most of the compounds also showed self-induced Aβ aggregation inhibitory activities, which were comparable or higher than those obtained for reference compounds, curcumin and myricetin. Docking and molecular dynamics (MD) simulation experiments suggested that the compounds are able to disrupt the dimer form of Aβ. Royal Society of Chemistry 2018 Article PeerReviewed Sukumaran, Sri Devi and Faraj, Fadhil Lafta and Lee, Vannajan Sanghiran and Othman, Rozana and Buckle, Michael James Christopher (2018) 2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones as inhibitors of cholinesterases and self-induced β-amyloid (Aβ) aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations. RSC Advances, 8 (14). pp. 7818-7831. ISSN 2046-2069, DOI https://doi.org/10.1039/c7ra11872d <https://doi.org/10.1039/c7ra11872d>. https://doi.org/10.1039/c7ra11872d doi:10.1039/c7ra11872d |
| spellingShingle | Q Science (General) QD Chemistry R Medicine Sukumaran, Sri Devi Faraj, Fadhil Lafta Lee, Vannajan Sanghiran Othman, Rozana Buckle, Michael James Christopher 2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones as inhibitors of cholinesterases and self-induced β-amyloid (Aβ) aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations |
| title | 2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones as inhibitors of cholinesterases and self-induced β-amyloid (Aβ) aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations |
| title_full | 2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones as inhibitors of cholinesterases and self-induced β-amyloid (Aβ) aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations |
| title_fullStr | 2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones as inhibitors of cholinesterases and self-induced β-amyloid (Aβ) aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations |
| title_full_unstemmed | 2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones as inhibitors of cholinesterases and self-induced β-amyloid (Aβ) aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations |
| title_short | 2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones as inhibitors of cholinesterases and self-induced β-amyloid (Aβ) aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations |
| title_sort | 2 aryl 3 arylideneamino 1 2 dihydroquinazoline 4 3h ones as inhibitors of cholinesterases and self induced β amyloid aβ aggregation biological evaluations and mechanistic insights from molecular dynamics simulations |
| topic | Q Science (General) QD Chemistry R Medicine |
| work_keys_str_mv | AT sukumaransridevi 2aryl3arylideneamino12dihydroquinazoline43honesasinhibitorsofcholinesterasesandselfinducedbamyloidabaggregationbiologicalevaluationsandmechanisticinsightsfrommoleculardynamicssimulations AT farajfadhillafta 2aryl3arylideneamino12dihydroquinazoline43honesasinhibitorsofcholinesterasesandselfinducedbamyloidabaggregationbiologicalevaluationsandmechanisticinsightsfrommoleculardynamicssimulations AT leevannajansanghiran 2aryl3arylideneamino12dihydroquinazoline43honesasinhibitorsofcholinesterasesandselfinducedbamyloidabaggregationbiologicalevaluationsandmechanisticinsightsfrommoleculardynamicssimulations AT othmanrozana 2aryl3arylideneamino12dihydroquinazoline43honesasinhibitorsofcholinesterasesandselfinducedbamyloidabaggregationbiologicalevaluationsandmechanisticinsightsfrommoleculardynamicssimulations AT bucklemichaeljameschristopher 2aryl3arylideneamino12dihydroquinazoline43honesasinhibitorsofcholinesterasesandselfinducedbamyloidabaggregationbiologicalevaluationsandmechanisticinsightsfrommoleculardynamicssimulations |