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

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

doi:10.1016/j.bmcl.2013.01.042

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

Bioorg Med Chem Lett. 2013 Mar 15;23(6):1789-92. doi: 10.1016/j.bmcl.2013.01.042. Epub 2013 Jan 22.

Authors

Gergely Varga¹, Tibor Docsa, Pál Gergely, László Juhász, László Somsák

Affiliation

¹ Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, PO Box 20, H-4010 Debrecen, Hungary.

PMID: 23395662
DOI: 10.1016/j.bmcl.2013.01.042

Abstract

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).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Allosteric Site
Animals
Cinnamates / chemistry*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / metabolism
Glutarates / chemistry*
Glycogen Phosphorylase, Muscle Form / antagonists & inhibitors*
Glycogen Phosphorylase, Muscle Form / metabolism
Hypoglycemic Agents / chemical synthesis*
Hypoglycemic Agents / chemistry
Protein Binding
Rabbits
Tartrates / chemical synthesis
Tartrates / chemistry*
Tartrates / metabolism

Substances

Cinnamates
Enzyme Inhibitors
FR258900
Glutarates
Hypoglycemic Agents
Tartrates
Glycogen Phosphorylase, Muscle Form
tartaric acid