Synthesis of tartaric acid analogues of FR258900 and their evaluation as glycogen phosphorylase inhibitors.

Gergely Varga, Tibor Docsa, Pál Gergely, László Juhász, László Somsák

Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, PO Box 20, H-4010 Debrecen, Hungary.

Bioorganic & medicinal chemistry letters 2013 Mar 15

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Di-O-cinnamoylated, -p-coumaroylated, and -feruloylated d-, l- and meso-tartaric acids were synthesized as analogues of the natural product FR258900, a glycogen phosphorylase (GP) inhibitor with in vivo antihyperglycaemic activity. The new compounds inhibited rabbit muscle GP in the low micromolar range, and bound to the allosteric site of the enzyme. The best inhibitor was 2,3-di-O-feruloyl meso-tartaric acid and had Ki values of 2.0μM against AMP (competitive) and 3.36μM against glucose-1-phosphate (non-competitive). Copyright © 2013 Elsevier Ltd. All rights reserved.

Citation

Gergely Varga, Tibor Docsa, Pál Gergely, László Juhász, László Somsák. Synthesis of tartaric acid analogues of FR258900 and their evaluation as glycogen phosphorylase inhibitors. Bioorganic & medicinal chemistry letters. 2013 Mar 15;23(6):1789-92