2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3 H)-ones as inhibitors of cholinesterases and self-induced β-amyloid (Aβ) aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations

Sri Devi Sukumaran; Fadhil Lafta Faraj; Vannajan Sanghiran Lee; Rozana Othman; Michael J C Buckle

doi:10.1039/c7ra11872d

2-Aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3 H)-ones as inhibitors of cholinesterases and self-induced β-amyloid (Aβ) aggregation: biological evaluations and mechanistic insights from molecular dynamics simulations

RSC Adv. 2018 Feb 19;8(14):7818-7831. doi: 10.1039/c7ra11872d. eCollection 2018 Feb 14.

Authors

Sri Devi Sukumaran^{1

2}, Fadhil Lafta Faraj³, Vannajan Sanghiran Lee^{2

4}, Rozana Othman^{1

2}, Michael J C Buckle^{1

2}

Affiliations

¹ Department of Pharmacy, Faculty of Medicine, University of Malaya 50603 Kuala Lumpur Malaysia shivanesri@yahoo.com buckle@um.edu.my rozanaothman@um.edu.my +60-3-7967-4959.
² Drug Design and Development Research Group (DDDRG), University of Malaya 50603 Kuala Lumpur Malaysia.
³ Department of Chemistry, Faculty of Science, University of Diyala Diyala Governorate Iraq fadhillaftafaraj@gmail.com.
⁴ Department of Chemistry, Faculty of Science, University of Malaya 50603 Kuala Lumpur Malaysia Vannajan@um.edu.my +60 163208906.

Abstract

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.