title: Synthesis of tartaric acid analogues of FR258900 and their evaluation as glycogen phosphorylase inhibitors.
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).
authors: Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, PO Box 20, H-4010 Debrecen, Hungary.
authors: Gergely
authors: G
authors: Varga
authors: Tibor
authors: T
authors: Docsa
authors: Pál
authors: P
authors: Gergely
authors: László
authors: L
authors: Juhász
authors: László
authors: L
authors: Somsák
mesh_terms: D000495:Allosteric Site; D000818:Animals; D002934:Cinnamates / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D005977:Glutarates / Q000737:chemistry*; D024982:Glycogen Phosphorylase, Muscle Form / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D011485:Protein Binding; D011817:Rabbits; D013644:Tartrates / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002934:Cinnamates; D004791:Enzyme Inhibitors; C506313:FR258900; D005977:Glutarates; D007004:Hypoglycemic Agents; D013644:Tartrates; D024982:Glycogen Phosphorylase, Muscle Form; C029768:tartaric acid