Amaryllidaceae Alkaloids As Potential Glycogen Synthase Kinase-3β Inhibitors

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2018 Mar 22

PMID 29561817

Citations 7

Authors

Daniela Hulcova

Katerina Breiterova

Tomas Siatka

Kamila Klimova

Lara Davani

Marcela Safratova

Anna Hostalkova

Angela De Simone

Vincenza Andrisano

Lucie Cahlikova

Affiliations

Soon will be listed here.

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--demethylhomolycorine (IC = 30.00 ± 0.71 µM), masonine (IC = 27.81 ± 0.01 μM)}, and lycorine-types {caranine (IC = 30.75 ± 0.04 μM)}.

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