Abstract
Glycogen synthase kinase-3 beta (GSK-3 beta) 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 beta-catenin.
Recent studies have identified GSK-3 beta as a potential therapeutic target in Alzheimer's disease, bipolar disorder, stroke, more than 15 types of cancer, and diabetes. GSK-3 beta 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-3 beta. Promising results have been demonstrated by alkaloids of the homolycorine-{9-O-demethylhomolycorine (IC50 = 30.00 +/- 0.71 mu M), masonine (IC50 = 27.81 +/- 0.01 mu M)}, and lycorine-types {caranine (IC50 = 30.75 +/- 0.04 mu M)}.