title: Isoquinoline Alkaloids from Fumaria officinalis L. and Their Biological Activities Related to Alzheimer's Disease.
abstract: Two new isoquinoline alkaloids, named fumaranine (2) and fumarostrejdine (10), along with 18 known alkaloids were isolated from aerial parts of Fumaria officinalis. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses and by comparison with literature data. The absolute configuration of the new compound 2 was determined by comparing its circular dichroism spectra with those of known analogs. Compounds isolated in sufficient amounts were evaluated for their acetylcholinesterase, butyrylcholinesterase, prolyl oligopeptidase (POP), and glycogen synthase kinase-3β inhibitory activities. Parfumidine (8) and sinactine (15) exhibited potent POP inhibition activities (IC50 99±5 and 53±2 μM, resp.).
authors.affiliation: ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, (phone: +420-495-067311; fax: +420-495-067162).
authors.forename: Jakub
authors.initials: J
authors.lastname: Chlebek
authors.affiliation: Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Novák
authors.affiliation: ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, (phone: +420-495-067311; fax: +420-495-067162).
authors.forename: Dominika
authors.initials: D
authors.lastname: Kassemová
authors.affiliation: ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, (phone: +420-495-067311; fax: +420-495-067162).
authors.forename: Marcela
authors.initials: M
authors.lastname: Šafratová
authors.affiliation: ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, (phone: +420-495-067311; fax: +420-495-067162).
authors.forename: Jan
authors.initials: J
authors.lastname: Kostelník
authors.affiliation: ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, (phone: +420-495-067311; fax: +420-495-067162).
authors.forename: Lukáš
authors.initials: L
authors.lastname: Malý
authors.affiliation: ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, (phone: +420-495-067311; fax: +420-495-067162).
authors.forename: Miroslav
authors.initials: M
authors.lastname: Ločárek
authors.affiliation: ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, (phone: +420-495-067311; fax: +420-495-067162).
authors.forename: Lubomír
authors.initials: L
authors.lastname: Opletal
authors.affiliation: ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, (phone: +420-495-067311; fax: +420-495-067162).
authors.forename: Anna
authors.initials: A
authors.lastname: Hošt'álková
authors.affiliation: Centre of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Třebešská 1575, CZ-500 05 Hradec Králové
authors.forename: Martina
authors.initials: M
authors.lastname: Hrabinová
authors.affiliation: Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové
authors.forename: Jiří
authors.initials: J
authors.lastname: Kuneš
authors.affiliation: Department of Physics and Measurements, Department of Analytical Chemistry, Institute of Chemical Technology, Prague, Technická 5, CZ-166 28 Prague.
authors.forename: Pavlína
authors.initials: P
authors.lastname: Novotná
authors.affiliation: Department of Physics and Measurements, Department of Analytical Chemistry, Institute of Chemical Technology, Prague, Technická 5, CZ-166 28 Prague.
authors.forename: Marie
authors.initials: M
authors.lastname: Urbanová
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové
authors.forename: Lucie
authors.initials: L
authors.lastname: Nováková
authors.affiliation: ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, (phone: +420-495-067311; fax: +420-495-067162).
authors.forename: Kateřina
authors.initials: K
authors.lastname: Macáková
authors.affiliation: ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, (phone: +420-495-067311; fax: +420-495-067162).
authors.forename: Daniela
authors.initials: D
authors.lastname: Hulcová
authors.affiliation: Department of Physics and Measurements, Department of Analytical Chemistry, Institute of Chemical Technology, Prague, Technická 5, CZ-166 28 Prague.
authors.forename: Petr
authors.initials: P
authors.lastname: Solich
authors.affiliation: Instituto de Química Medica-CSIC, Juan de la Cierva 3, ES-28006 Madrid.
authors.forename: Concepción
authors.initials: C
authors.lastname: Pérez Martín
authors.affiliation: Centre of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Třebešská 1575, CZ-500 05 Hradec Králové
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.affiliation: ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, (phone: +420-495-067311; fax: +420-495-067162). cahlikova@faf.cuni.cz.
authors.forename: Lucie
authors.initials: L
authors.lastname: Cahlíková
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D031312:Fumaria / Q000737:chemistry*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D004791:Enzyme Inhibitors; D007546:Isoquinolines; C000611413:fumaranine; C000611412:fumarostrejdine; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases
keywords: Acetylcholinesterase; Butyrylcholinesterase; Fumaria officinalis; Glycogen synthase kinase-3β; Isoquinoline alkaloids; Prolyl oligopeptidase