Amaryllidaceae Alkaloids as Potential Glycogen Synthase Kinase-3β Inhibitors

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)}.

Medicinal Plants to Strengthen Immunity during a Pandemic

“…( Amaryllidaceae ) originally grew in China, Korea and Nepal and was later distributed to other countries, including Russia. It is a source of pharmacologically active alkaloids, with lycorine being the main one [ 11 , 23 , 24 , 25 , 26 ]. Lycorine has selective antiviral activity, including against severe acute respiratory syndrome associated with coronavirus and influenza virus [ 11 , 21 , 27 ].…”

Derivatives of the β-Crinane Amaryllidaceae Alkaloid Haemanthamine as Multi-Target Directed Ligands for Alzheimer’s Disease

“…Selected haemanthamine derivatives (compounds 1g , 1j and 1m ) were screened for their GSK-3β inhibition potency at a concentration of 10 µM. Since 1m revealed the highest inhibition potency in the tested concentration scale, its IC 50 was further determined demonstrating a slightly less potent profile compared with the native Amaryllidaceae alkaloids masonine, caranine, and narcimatuline [39].…”

“…The GSK-3β assay was performed by using Kinase-Glo Kit obtained from Promega (Promega Biotech Iberica, SL, Madrid, Spain) as described previously [39].…”

Lycorine: A prospective natural lead for anticancer drug discovery

“…Amaryllidaceae family plants are well known as an extensive source of pharmacologically active alkaloids [10][11][12][13], and lycorine was the first among these alkaloids to be isolated in 1877 from the plant Narcissus pseudonarcissus [14]. From then onwards, lycorine and its derivatives are drawing interest in the medicinal field due to their divergent chemical structures and strong biological effects [ Fig.…”