title: Kinetics and molecular docking studies of cholinesterase inhibitors derived from water layer of Lycopodiella cernua (L.) Pic. Serm. (II).
abstract: Acetylcholinesterase (AChE) inhibitors increase the availability of acetylcholine in central cholinergic synapses and are the most promising drugs currently available for the treatment of Alzheimer's disease (AD). Our screening study indicated that the water fraction of the methanolic extract of Lycopodiella cernua (L.) Pic. Serm. significantly inhibited AChE in vitro. Bioassay-guided fractionation led to the isolation of a new lignan glycoside, lycocernuaside A (12), and fourteen known compounds (1-11 and 13-15). Compound 7 exhibited the most potent AChE inhibitory activity with an IC50 value of 0.23 μM. Compound 15 had the most potent inhibitory activity against BChE and BACE1 with IC50 values of 0.62 and 2.16 μM, respectively. Compounds 4 and 7 showed mixed- and competitive-type AChE inhibition. Compound 7 noncompetitively inhibited BChE whereas 15 showed competitive and 8, 13, and 14 showed mixed-type inhibition. The docking results for complexes with AChE or BChE revealed that inhibitors 4, 7, and 15 stably positioned themselves in several pocket/catalytic domains of the AChE and BChE residues.
authors: College of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongbuk 712-702, South Korea; Division of Pharmaceutical Chemistry, Faculty of Chemistry, University of Science, Vietnam National University-HoChiMinh City, 227 Nguyen Van Cu Street, District 5, HoChiMinh City, Viet Nam.
authors: Tran Manh
authors: TM
authors: Hung
authors: College of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongbuk 712-702, South Korea.
authors: Joo Sang
authors: JS
authors: Lee
authors: Faculty of Traditional Medicine, HoChiMinh City University of Medicine and Pharmacy, 221B Hoang Van Thu Street, Phu Nhuan District, HoChiMinh City, Viet Nam.
authors: Nguyen Ngoc
authors: NN
authors: Chuong
authors: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, South Korea.
authors: Jeong Ah
authors: JA
authors: Kim
authors: Korean BioInformation Center (KOBIC), Daejeon 305-806, South Korea.
authors: Sang Ho
authors: SH
authors: Oh
authors: College of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongbuk 712-702, South Korea.
authors: Mi Hee
authors: MH
authors: Woo
authors: Department of Food and Life Science, Pukyong National University, Busan 608-737, South Korea.
authors: Jae Sue
authors: JS
authors: Choi
authors: College of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongbuk 712-702, South Korea. Electronic address: bsmin@cu.ac.kr.
authors: Byung Sun
authors: BS
authors: Min
mesh_terms: D001667:Binding, Competitive; D001681:Biological Assay; D005591:Chemical Fractionation; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006027:Glycosides / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D017705:Lignans / Q000737:chemistry* / Q000494:pharmacology; D029542:Lycopodiaceae / Q000737:chemistry*; D000432:Methanol / Q000737:chemistry; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D014867:Water / Q000737:chemistry*
chemical_list: D002800:Cholinesterase Inhibitors; D006027:Glycosides; D017705:Lignans; D010936:Plant Extracts; D014867:Water; D000432:Methanol
keywords: AChEs; Docking; Lignan glycoside; Lycopodiaceae; Lycopodiella cernua