title: Flavonoids with M1 muscarinic acetylcholine receptor binding activity.
abstract: Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer's disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki=40-110 µM), comparable to that of acetylcholine (Ki=59 µM). Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.
authors: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. oosh_mey@yahoo.com.
authors: Meyyammai
authors: M
authors: Swaminathan
authors: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. cfchee@yahoo.com.
authors: Chin Fei
authors: CF
authors: Chee
authors: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. xueping.chin@gmail.com.
authors: Sek Peng
authors: SP
authors: Chin
authors: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. buckle@um.edu.my.
authors: Michael J C
authors: MJ
authors: Buckle
authors: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. noorsaadah@um.edu.my.
authors: Noorsaadah Abd
authors: NA
authors: Rahman
authors: School of Pharmacy, University of Nottingham Malaysia Campus, Jalan Broga, 43500 Semenyih, Selangor Darul Ehsan, Malaysia. stephen.doughty@nottingham.edu.my.
authors: Stephen W
authors: SW
authors: Doughty
authors: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. chungly@um.edu.my.
authors: Lip Yong
authors: LY
authors: Chung
mesh_terms: D000818:Animals; D001665:Binding Sites; D047309:Flavones / Q000737:chemistry*; D062105:Molecular Docking Simulation; D018721:Muscarinic Agonists / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D043643:Receptor, Muscarinic M1 / Q000737:chemistry*
chemical_list: D047309:Flavones; D018721:Muscarinic Agonists; D043643:Receptor, Muscarinic M1