N-(Β-D-Glucopyranosyl)-Azolecarboxamides as Glycogen Phosphorylase Inhibitors: Computational Prediction, Synthesis and Enzymatic Evaluation

PS2 Poster session 2 Even numbers
Location (hall): 
Start/end time: 
Tuesday, July 2, 2019 - 15:45 to 17:15

Levente Homolya1, Rachel Mathomes2, Ádám Sipos3, Tibor Docsa3, László Juhász1, Joseph M. Hayes2, László Somsák1

1Department of Organic Chemistry, University of Debrecen, Debrecen, Hungary, 2School of Pharmacy & Biomedical Sciences, University of Central Lancashire, Preston, United Kingdom, 3Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

Type II diabetes mellitus characterized by hyperglycemia and peripheral insulin resistance is one of the major concerns of our society [1]. Since the disease is not curable, without the control of blood glucose levels serious complications may appear, therefore, the most important task in the treatment of diabetes mellitus is to normalize blood glucose levels. Glycogen phosphorylase (GP) is the rate determining enzyme of glycogen metabolism, therefore its inhibitors are potential antidiabetic agents.

Several compounds, with potential GP inhibitor activity were synthesized earlier, such as N-(β-D-glucopyranosyl)-aryl-oxadiazolecarboxamides (aryl: phenyl, 1-naphthyl, 2-naphthyl) and N-(β-D-glucopyranosyl)-5-aryl-1,2,4-triazole-3-carboxamides (aryl: phenyl, 2-naphthyl) [2, 3]. In continuation of this research, based on the computational prediction of GP inhibitor activities of new molecules, the synthesis of N-(β-D-glucopyranosyl)-5-(1-naphthyl)-1,2,4-triazole-3-carboxamide (2c), N-(β-D-glucopyranosyl)-2-arylimidazole-4(5)-carboxamide (3a-c) and N-(β-D-glucopyranosyl)-4(5)-arylimidazole-2-carboxamide (4a-c) (aryl: phenyl, 1-naphthyl, 2-naphthyl) were planned and performed. Details of the syntheses and enzyme kinetic results will be presented on the poster.

Figure 1.: Structure of N-(β-D-glucopyranosyl)-azolecarboxamides

  1. Karuranga, S.; Fernandes, J. R.; Huang, Y.; Malanda, B.; IDF Diabetes Atlas – 8th edition, International Diabetes Federation, 2017.
  2. Polyák, M.; Varga, G.; Szilágyi, B.; Juhász, L.; Docsa, T.; Gergely, P.; Begum, J.; Hayes, J. M.; Somsák, L.; Bioorganic & Medicinal Chemistry, 2013, 21, 5738.
  3. Begum, J.; Varga, G.; Docsa, T.; Gergely, P.; Hayes, J. M.; Juhász, L.; Somsák.L.; MedChemComm, 2015, 6, 80.