title: Isolation of cholinesterase and β-secretase 1 inhibiting compounds from Lycopodiella cernua.
abstract: Three new serratene-type triterpenoids (1-3) and a new hydroxy unsaturated fatty acid (13) together with nine known compounds (4-12) were isolated from Lycopodiella cernua. The chemical structures were established using NMR, MS, and Mosher's method. Compound 13 showed the most potent inhibitory activity against acetylcholinesterase (AChE) with an IC50 value of 0.22μM. For butyrylcholinesterase (BChE) inhibitory activity, 5 showed the most potent activity with an IC50 value of 0.42μM. Compound 2 showed the most potent activity with an IC50 of 0.23μM for BACE-1 inhibitory activity. The kinetic activities were investigated to determine the type of enzyme inhibition involved. The types of AChE inhibition shown by compounds 4, 5, and 13 were mixed; BChE inhibition by 5 was competitive, while 2 and 6 showed mixed-types. In addition, molecular docking studies were performed to investigate the interaction of these compounds with the pocket sites of AChE. The docking results revealed that the tested inhibitors 3, 4, and 13 were stably present in several pocket domains of the AChE residue.
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongbuk 712-702, Republic of Korea.
authors.forename: Van Thu
authors.initials: VT
authors.lastname: Nguyen
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongbuk 712-702, Republic of Korea.
authors.forename: Dao Cuong
authors.initials: DC
authors.lastname: To
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongbuk 712-702, Republic of Korea.
authors.forename: Manh Hung
authors.initials: MH
authors.lastname: Tran
authors.affiliation: Korean Bioinformation Center (KOBIC), Daejeon 305-806, Republic of Korea.
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Jeong Ah
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Faculty of Food Science and Biotechnology, Pukyung National University, Busan 608-737, Republic of Korea.
authors.forename: Md Yousof
authors.initials: MY
authors.lastname: Ali
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongbuk 712-702, Republic of Korea.
authors.forename: Mi-Hee
authors.initials: MH
authors.lastname: Woo
authors.affiliation: Faculty of Food Science and Biotechnology, Pukyung National University, Busan 608-737, Republic of Korea.
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongbuk 712-702, Republic of Korea. Electronic address: bsmin@cu.ac.kr.
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Min
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002091:Butyrylcholinesterase / Q000737:chemistry*; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D029542:Lycopodiaceae / Q000737:chemistry*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry; D011480:Protease Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D002800:Cholinesterase Inhibitors; D005231:Fatty Acids, Unsaturated; D010936:Plant Extracts; D011480:Protease Inhibitors; D014315:Triterpenes; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: Cholinesterase; Hydroxy unsaturated fatty acid; Lycopodiella cernua; Serratene-type triterpenoids; β-Secretase