5o54 › Citations

Nanomolar Inhibitors of Glycogen Phosphorylase Based on β-d-Glucosaminyl Heterocycles: A Combined Synthetic, Enzyme Kinetic, and Protein Crystallography Study.

Bokor É, Kyriakis E, Solovou TGA, Koppány C, Kantsadi AL, Szabó KE, Szakács A, Stravodimos GA, Docsa T, Skamnaki VT, Zographos SE, Gergely P, Leonidas DD, Somsák L
J Med Chem 60 9251-9262 (2017)
Related entries: 5o50, 5o52, 5o56

Cited: 7 times
EuropePMC logo PMID: 28925695

Abstract

Aryl substituted 1-(β-d-glucosaminyl)-1,2,3-triazoles as well as C-β-d-glucosaminyl 1,2,4-triazoles and imidazoles were synthesized and tested as inhibitors against muscle and liver isoforms of glycogen phosphorylase (GP). While the N-β-d-glucosaminyl 1,2,3-triazoles showed weak or no inhibition, the C-β-d-glucosaminyl derivatives had potent activity, and the best inhibitor was the 2-(β-d-glucosaminyl)-4(5)-(2-naphthyl)-imidazole with a Ki value of 143 nM against human liver GPa. An X-ray crystallography study of the rabbit muscle GPb inhibitor complexes revealed structural features of the strong binding and offered an explanation for the differences in inhibitory potency between glucosyl and glucosaminyl derivatives and also for the differences between imidazole and 1,2,4-triazole analogues.

Reviews citing this publication (1)

  1. Tetrazoles and Related Heterocycles as Promising Synthetic Antidiabetic Agents. Trifonov RE, Ostrovskii VA. Int J Mol Sci 24 17190 (2023)

Articles citing this publication (6)

  1. Optimization and Validation of an In Vitro Standardized Glycogen Phosphorylase Activity Assay. Rocha S, Lucas M, Araújo AN, Corvo ML, Fernandes E, Freitas M. Molecules 26 4635 (2021)
  2. BIM-46174 fragments as potential ligands of G proteins. Küppers J, Benkel T, Annala S, Schnakenburg G, Kostenis E, Gütschow M. Medchemcomm 10 1838-1843 (2019)
  3. First Synthesis of 3-Glycopyranosyl-1,2,4-Triazines and Some Cycloadditions Thereof. Bokor É, Ferenczi A, Hashimov M, Juhász-Tóth É, Götz Z, Zaki AI, Somsák L. Molecules 27 7801 (2022)
  4. Glycogen phosphorylase revisited: extending the resolution of the R- and T-state structures of the free enzyme and in complex with allosteric activators. Leonidas DD, Zographos SE, Tsitsanou KE, Skamnaki VT, Stravodimos G, Kyriakis E. Acta Crystallogr F Struct Biol Commun 77 303-311 (2021)
  5. Gram scale production of 1-azido-β-d-glucose via enzyme catalysis for the synthesis of 1,2,3-triazole-glucosides. Gorantla JN, Pengthaisong S, Choknud S, Kaewpuang T, Manyum T, Promarak V, Ketudat Cairns JR. RSC Adv 9 6211-6220 (2019)
  6. Outliers in SAR and QSAR: 4. effects of allosteric protein-ligand interactions on the classical quantitative structure-activity relationships. Kim KH. Mol Divers (2022)


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