Isoquinoline Alkaloids from Fumaria officinalis L. and Their Biological Activities Related to Alzheimer's Disease

Jakub Chlebek; Zdeněk Novák; Dominika Kassemová; Marcela Šafratová; Jan Kostelník; Lukáš Malý; Miroslav Ločárek; Lubomír Opletal; Anna Hošt'álková; Martina Hrabinová; Jiří Kuneš; Pavlína Novotná; Marie Urbanová; Lucie Nováková; Kateřina Macáková; Daniela Hulcová; Petr Solich; Concepción Pérez Martín; Daniel Jun; Lucie Cahlíková

doi:10.1002/cbdv.201500033

Isoquinoline Alkaloids from Fumaria officinalis L. and Their Biological Activities Related to Alzheimer's Disease

Chem Biodivers. 2016 Jan;13(1):91-9. doi: 10.1002/cbdv.201500033.

Authors

Jakub Chlebek¹, Zdeněk Novák², Dominika Kassemová¹, Marcela Šafratová¹, Jan Kostelník¹, Lukáš Malý¹, Miroslav Ločárek¹, Lubomír Opletal¹, Anna Hošt'álková¹, Martina Hrabinová³, Jiří Kuneš², Pavlína Novotná⁴, Marie Urbanová⁴, Lucie Nováková⁵, Kateřina Macáková¹, Daniela Hulcová¹, Petr Solich⁴, Concepción Pérez Martín⁶, Daniel Jun³, Lucie Cahlíková⁷

Affiliations

¹ 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).
² Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové
³ Centre of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Třebešská 1575, CZ-500 05 Hradec Králové
⁴ Department of Physics and Measurements, Department of Analytical Chemistry, Institute of Chemical Technology, Prague, Technická 5, CZ-166 28 Prague.
⁵ Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové
⁶ Instituto de Química Medica-CSIC, Juan de la Cierva 3, ES-28006 Madrid.
⁷ 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.

PMID: 26765356
DOI: 10.1002/cbdv.201500033

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.).

Keywords: Acetylcholinesterase; Butyrylcholinesterase; Fumaria officinalis; Glycogen synthase kinase-3β; Isoquinoline alkaloids; Prolyl oligopeptidase.

MeSH terms

Acetylcholinesterase / metabolism
Alkaloids / chemistry
Alkaloids / isolation & purification
Alkaloids / pharmacology*
Alzheimer Disease / drug therapy*
Alzheimer Disease / enzymology
Butyrylcholinesterase / metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / pharmacology*
Fumaria / chemistry*
Glycogen Synthase Kinase 3 / antagonists & inhibitors
Glycogen Synthase Kinase 3 / metabolism
Glycogen Synthase Kinase 3 beta
Humans
Isoquinolines / chemistry
Isoquinolines / isolation & purification
Isoquinolines / pharmacology*
Molecular Structure
Prolyl Oligopeptidases
Serine Endopeptidases / metabolism
Structure-Activity Relationship

Substances

Alkaloids
Enzyme Inhibitors
Isoquinolines
fumaranine
fumarostrejdine
GSK3B protein, human
Glycogen Synthase Kinase 3 beta
Glycogen Synthase Kinase 3
Acetylcholinesterase
Butyrylcholinesterase
Serine Endopeptidases
PREPL protein, human
Prolyl Oligopeptidases