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Molecules. 2018 Mar 21;23(4). pii: E719. doi: 10.3390/molecules23040719.

Amaryllidaceae Alkaloids as Potential Glycogen Synthase Kinase-3β Inhibitors.

Author information

1
ADINACO Research Group, Department of Pharmacognosy, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic. hulcovd@faf.cuni.cz.
2
Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic. hulcovd@faf.cuni.cz.
3
Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic. breiterk@faf.cuni.cz.
4
ADINACO Research Group, Department of Pharmacognosy, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic. siatka@faf.cuni.cz.
5
Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic. kklimova000@gmail.com.
6
Department for Life Quality Studies, University of Bologna, 47921 Rimini, Italy. lorisdavani@libero.it.
7
ADINACO Research Group, Department of Pharmacognosy, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic. safratom@faf.cuni.cz.
8
Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic. hosta4aa@faf.cuni.cz.
9
Department for Life Quality Studies, University of Bologna, 47921 Rimini, Italy. angela.desimone2@unibo.it.
10
Department for Life Quality Studies, University of Bologna, 47921 Rimini, Italy. vincenza.andrisano@unibo.it.
11
Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic. cahlikova@faf.cuni.cz.

Abstract

Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine protein kinase that was originally identified as an enzyme involved in the control of glycogen metabolism. It plays a key role in diverse physiological processes including metabolism, the cell cycle, and gene expression by regulating a wide variety of well-known substances like glycogen synthase, tau-protein, and β-catenin. Recent studies have identified GSK-3β as a potential therapeutic target in Alzheimer´s disease, bipolar disorder, stroke, more than 15 types of cancer, and diabetes. GSK-3β is one of the most attractive targets for medicinal chemists in the discovery, design, and synthesis of new selective potent inhibitors. In the current study, twenty-eight Amaryllidaceae alkaloids of various structural types were studied for their potency to inhibit GSK-3β. Promising results have been demonstrated by alkaloids of the homolycorine-{9-O-demethylhomolycorine (IC50 = 30.00 ± 0.71 µM), masonine (IC50 = 27.81 ± 0.01 μM)}, and lycorine-types {caranine (IC50 = 30.75 ± 0.04 μM)}.

KEYWORDS:

9-O-demethylhomolycorine; Alzheimer’s disease; Amaryllidaceae alkaloids; caranine; glycogen synthase kinase-3β; masonine

PMID:
29561817
DOI:
10.3390/molecules23040719
[Indexed for MEDLINE]
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