title: Synthesis, Biological Evaluation and Molecular Modelling of 2'-Hydroxychalcones as Acetylcholinesterase Inhibitors.
abstract: 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.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. shivanesri@yahoo.com.
authors.forename: Sri Devi
authors.initials: SD
authors.lastname: Sukumaran
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. cfchee@yahoo.com.|Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. cfchee@yahoo.com.
authors.forename: Chin Fei
authors.initials: CF
authors.lastname: Chee
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. geethaviswa@gmail.com.
authors.forename: Geetha
authors.initials: G
authors.lastname: Viswanathan
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. buckle@um.edu.my.
authors.forename: Michael J C
authors.initials: MJ
authors.lastname: Buckle
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. rozanaothman@um.edu.my.
authors.forename: Rozana
authors.initials: R
authors.lastname: Othman
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. noorsaadah@um.edu.my.
authors.forename: Noorsaadah
authors.initials: N
authors.lastname: Abd Rahman
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. chungly@um.edu.my.
authors.forename: Lip Yong
authors.initials: LY
authors.lastname: Chung
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D001665:Binding Sites; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D006868:Hydrolysis; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D047188:Chalcones; D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; C013031:2'-hydroxychalcone
keywords: Alzheimer’s disease; acetylcholinesterase; chalcones; molecular modelling