Advances in glycogen phosphorylase inhibitor design

Current Opinion in Investigational Drugs

Volumn 9, Issue 4, 2008, Pages 379-395

  Oikonomakos, N G ^a   Somsak L ^b  

^a INSTITUTE OF BIOLOGY   (Greece)

^b UNIVERSITY OF DEBRECEN   (Hungary)

Author keywords

Antihyperglycemics; Drug design; Enzyme binding site; Glycogen phosphorylase inhibitor; Hyperglycemia; SAR; Type 2 diabetes; X ray crystallography

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; BENZAMIDE DERIVATIVE; C BETA D GLUCOPYRANOSYL; CINNAMIC ACID DERIVATIVE; CP 320626; DICHLOROCINNAMIC ACID DERIVATIVE; ENZYME INHIBITOR; FLAVONOID; GLYCINAMIDE; INDIRUBIN 3' AMINOOXY ACETATE; INDIRUBIN 5 SULFONATE; ISOFAGOMINE; N ACETYL BETA D GLUCOPYRANOSYLAMINE; N ARYL N' AROYL UREA; OLEANOLIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

BINDING SITE; CATALYSIS; DRUG DESIGN; DRUG INHIBITION; DRUG MECHANISM; ENZYME ACTIVE SITE; HYDROGEN BOND; REVIEW; X RAY CRYSTALLOGRAPHY;

ALLOSTERIC REGULATION; ALLOSTERIC SITE; ANIMALS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; ENZYME INHIBITORS; GLYCOGEN; GLYCOGEN PHOSPHORYLASE; HUMANS; HYPOGLYCEMIC AGENTS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN BINDING; PROTEIN CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP; TECHNOLOGY, PHARMACEUTICAL;

EID: 41949086319     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (54)

1. Green A, Christian Hirsch N, Pramming SK: The changing world demography of type 2 diabetes. Diabetes-Metab Res Rev (2003) 19(1):3-7.
2. Diamond J: The double puzzle of diabetes. Nature (2003) 423(6940):599-602.
3. Alberti G, Zimmet P, Shaw J, Bloomgarden Z, Kaufman F, Silink M: Type 2 diabetes in the young: The evolving epidemic: The international diabetes federation consensus workshop. Diabetes Care (2004) 27(7):1798-1811.
4. Ehtisham S, Barrett TG: The emergence of type 2 diabetes in childhood. Ann Clin Biochem (2004) 41(Pt 1):10-16.
5. Cheng AY, Fantus IG: Oral antihyperglycemic therapy for type 2 diabetes mellitus. Can Med Assoc J (2005) 172(2):213-226.
6. Krentz AJ, Bailey CJ: Oral antidiabetic agents - Current role in type 2 diabetes mellitus. Drugs (2005) 65(3):385-411.
7. van de Laar FA, Lucassen PL, Akkermans RP, van de Lisdonk FH, Rutten GE, van Weel C: α-Glucosidase inhibitors for patients with type 2 diabetes: Results from a cochrane systematic review and meta-analysis. Diabetes Care (2005) 28(1):154-163.
8. Morral N: Novel targets and therapeutic strategies for type 2 diabetes. Trends Endocrin Metab (2003) 14(4):169-175.
9. Agius L: New hepatic targets for glycaemic control in diabetes. Best Pract Res Clin Endocrinol Metab (2007) 21(4):587-605.
10. Lerín C, Montell E, Nolasco T, García-Rocha M, Guinovart JJ, Gómez-Foix AM: Regulation of glycogen metabolism in cultured human muscles by the glycogen phosphorylase inhibitor CP-91149. Biochem J (2004) 378(Pt 3):1073-1077.
11. Baker DJ, Timmons JA, Greenhaff PL: Glycogen phosphorylase inhibition in type 2 diabetes therapy - A systematic evaluation of metabolic and functional effects in rat skeletal muscle. Diabetes (2005) 54(8):2453- 2459.
12. Baker DJ, Greenhaff PL, MacInnes A, Timmons JA: The experimental type 2 diabetes therapy glycogen phosphorylase inhibition can impair aerobic muscle function during prolonged contraction. Diabetes (2006) 55(6):1855-1861.
13. Baker DJ, Greenhaff PL, Timmons JA: Glycogen phosphorylase inhibition as a therapeutic target: A review of the recent patent literature. Expert Opin Ther Patents (2006) 16(4):459-466.
14. Freeman S, Bartlett JB, Convey G, Hardern I, Teague JL, Loxham SJ, Allen JM, Poucher SM, Charles AD: Sensitivity of glycogen phosphorylase isoforms to indole site inhibitors is markedly dependent on the activation state of the enzyme. Brit J Pharmacol (2006) 149(6):775-785.
15. Oikonomakos NG: Glycogen phosphorylase as a molecular target for type 2 diabetes therapy. Curr Protein Pept Sci (2002) 3(6):561-586.
16. Somsák L, Nagy V, Hadady Z, Docsa T, Gergely P: Glucose analog inhibitors of glycogen phosphorylases as potential antidiabetic agents: Recent developments. Curr Pharma Des (2003) 9(15):1177-1189.
17. Henke BR, Sparks SM: Glycogen phosphorylase inhibitors. Mini-Rev Med Chem (2006) 6(8):845-857.
18. Anagnostou E, Kosmopoulou MN, Chrysina ED, Leonidas DD, Hadjiloi T, Tiraidis C, Zographos SE, Györgydeák Z, Somsák L, Docsa T, Gergely P et al: Crystallographic studies on two bioisosteric analogues, N-acetyl-β-D-glucopyranosylamine and N-trifluoroacetyl-β-D-glucopyranosylamine, potent inhibitors of muscle glycogen phosphorylase. Bioorg Med Chem (2006) 14(1):181-189.
19. Petsalakis EI, Chrysina ED, Tiraidis C, Hadjiloi T, Leonidas DD, Oikonomakos NG, Aich U, Varghese B, Loganathan D: Crystallographic studies on N-azidoacetyl-β-D-glucopyranosylamine, an inhibitor of glycogen phosphorylase: Comparison with N-acetyl- β-D-glucopyranosylamine. Bioorg Med Chem (2006) 14(15):5316-5324.
20. Györgydeák Z, Hadady Z, Felföldi N, Krakomperger A, Nagy V, Tóth M, Brunyánszki A, Docsa T, Gergely P, Somsák L: Synthesis of N-(β-D-glucopyranosyl)- and N-(2-acetamido-2-deoxy-β-D-glucopyranosyl) amides as inhibitors of glycogen phosphorylase. Bioorg Med Chem (2004) 12(18):4861- 4870. • The usefulness of large aromatic substituents next to the anomeric centre of glucose derivatives.
21. Czifrák K, Hadady Z, Docsa T, Gergely P, Schmidt J, Wessjohann L, Somsák L: Synthesis of N-(β-D- glucopyranosyl) monoamides of dicarboxylic acids as potential inhibitors of glycogen phosphorylase. Carbohydr Res (2006) 341(8):947-956.
22. Alexacou KM, Hayes JM, Tiraidis C, Zographos SE, Leonidas DD, Chrysina ED, Archontis G, Oikonomakos NG, Paul JV, Varghese B, Loganathan D: Crystallographic and computational studies on 4-phenyl-N-(β-D-glucopyranosyl)-1H-1,2, 3-triazole-1-acetamide, an inhibitor of glycogen phosphorylase: Comparison with α-D-glucose, N-acetyl-β-D- glucopyranosylamine and N-benzoyl-N′- β-D-glucopyranosyl urea binding. Proteins (2008) 71:301-317.
23. Chrysina ED, Kosmopoulou MN, Kardakaris R, Bischler N, Leonidas DD, Kannan T, Loganathan D, Oikonomakos NG: Binding of β-D- glucopyranosyl bismethoxyphosphoramidate to glycogen phosphorylase b: Kinetic and crystallographic studies. Bioorg Med Chem (2005) 13(3):765-772.
24. Hadjiloi T, Tiraidis C, Chrysina ED, Leonidas DD, Oikonomakos NG, Tsipos P, Gimisis T: Binding of oxalyl derivatives of β-D- glucopyranosylamine to muscle glycogen phosphorylase b. Bioorg Med Chem (2006) 14(11):3872-3882.
25. Watson KA, Chrysina ED, Tsitsanou KE, Zographos SE, Archontis G, Fleet GW, Oikonomakos NG: Kinetic and crystallographic studies of glucopyranose spirohydantoin and glucopyranosylamine analogs inhibitors of glycogen phosphorylase. Proteins (2005) 61(4):966-983.
26. Oikonomakos NG, Kosmopoulou M, Zographos SE, Leonidas DD, Chrysina ED, Somsák L, Nagy V, Praly JP, Docsa T, Tóth B, Gergely P: Binding of N-acetyl-N′-β-D- glucopyranosyl urea and N-benzoyl-N′- β-D-glucopyranosyl urea to glycogen phosphorylase b: Kinetic and crystallographic studies. Eur J Biochem (2002) 269(6):1684- 1696.
27. Hadady Z, Tóth M, Somsák L: C-(β-D- glucopyranosyl) heterocycles as potential glycogen phosphorylase inhibitors. Arkivoc (2004) (VII):140-149. • Description of the first inhibitors with a C-(β-D-glucopyranosyl)heterocycle structural element.
28. Chrysina ED, Kosmopoulou MN, Tiraidis C, Kardakaris R, Bischler N, Leonidas DD, Hadady Z, Somsak L, Docsa T, Gergely P, Oikonomakos NG: Kinetic and crystallographic studies on 2-(β-D-glucopyranosyl)-5-methyl-1, 3,4-oxadiazole, -benzothiazole, and -benzimidazole, inhibitors of muscle glycogen phosphorylase b. Evidence for a new binding site. Protein Sci (2005) 14(4):873-888. • This paper describes the structural requirements for tight binding of C-(β-D-glucopyranosyl) heterocyclic inhibitors.
29. Benltifa M, Vidal S, Gueyrard D, Goekjian PG, Msaddek M, Praly J-P: 1,3-Dipolar cycloaddition reactions on carbohydrate-based templates: Synthesis of spiro-isoxazolines and 1,2,4-oxadiazoles as glycogen phosphorylase inhibitors. Tetrahedron Lett (2006) 47(34):6143-6147. • Synthesis of new types of C-(β-D-glucopyranosyl)heterocyclic inhibitors.
30. Benltifa M, Vidal S, Fenet B, Msaddek M, Goekjian PG, Praly J-P, Brunyánszki A, Docsa T, Gergely P: In search of glycogen phosphorylase inhibitors: 5-Substituted 3-C-glucopyranosyl-1,2,4-oxadiazoles from β-D-glucopyranosyl cyanides upon cyclization of O-acyl-amidoxime intermediates. Eur J Org Chem (2006) (18):4242-4256.
31. Oikonomakos NG, Tiraidis C, Leonidas DD, Zographos SE, Kristiansen M, Jessen CU, Nørskov-Lauritsen L, Agius L: Iminosugars as potential inhibitors of glycogenolysis: Structural insights into the molecular basis of glycogen phosphorylase inhibition. J Med Chem (2006) 49(19):5687-5701. •• New synthesis for the first five-membered ring sugar analog (DAB) and iminosugars as R-state inhibitors of GP and a thorough study of structural peculiarities of binding.
32. Pinotsis N, Leonidas DD, Chrysina ED, Oikonomakos NG, Mavridis IM: The binding of β- and γ-cyclodextrins to glycogen phosphorylase b: Kinetic and crystallographic studies. Protein Sci (2003) 12(9):1914-1924.
33. Kosmopoulou MN, Leonidas DD, Chrysina ED, Bischler N, Eisenbrand G, Sakarellos CE, Pauptit R, Oikonomakos NG: Binding of the potential antitumour agent indirubin-5-sulphonate at the inhibitor site of rabbit muscle glycogen phosphorylase b. Comparison with ligand binding to pCDK2-cyclin A complex. Eur J Biochem (2004) 271(11):2280-2290.
34. Kosmopoulou MN, Leonidas DD, Chrysina ED, Oikonomakos NG, Eisenbrand G: Indirubin-3′-aminooxy-acetate inhibits glycogen phosphorylase by binding at the inhibitor and the allosteric site. Broad specificities of the two sites. Lett Drug Design Discov (2005) 2(5):377-390.
35. Hampson LJ, Arden C, Agius L, Ganotidis M, Kosmopoulou MN, Tiraidis C, Elemes Y, Sakarellos C, Leonidas DD, Oikonomakos NG: Bioactivity of glycogen phosphorylase inhibitors that bind to the purine nucleoside site. Bioorg Med Chem (2006) 14(23):7835-7845.
36. Klabunde T, Wendt KU, Kadereit D, Brachvogel V, Burger HJ, Herling AW, Oikonomakos NG, Kosmopoulou MN, Schmoll D, Sarubbi E, von Roedern E et al: Acyl ureas as human liver glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. J Med Chem (2005) 48(20):6178- 6193. •• This paper describes the parallel synthesis of a novel class of GP inhibitors with nanomolar cellular activity.
37. Oikonomakos NG, Kosmopoulou MN, Chrysina ED, Leonidas DD, Kostas ID, Wendt KU, Klabunde T, Defossa E: Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugs. Protein Sci (2005) 14(7):1760-1771.
38. Kristiansen M, Andersen B, Iversen LF, Westergaard N: Identification, synthesis, and characterization of new glycogen phosphorylase inhibitors binding to the allosteric AMP site. J Med Chem (2004) 47(14):3537- 3545. •• This paper describes the synthesis of a novel class of GP inhibitors for the allosteric site.
39. Lu Z, Bohn J, Bergeron R, Deng Q, Ellsworth KP, Geissler WM, Harris G, McCann PE, McKeever B, Myers RW, Saperstein R et al: A new class of glycogen phosphorylase inhibitors. Bioorg Med Chem Lett (2003) 13(22):4125-4128. •• Phthalic acid derivatives with significant selectivity in the inhibition of the liver vs. muscle enzyme.
40. Ogawa AK, Willoughby CA, Bergeron R, Ellsworth KP, Geissler WM, Myers RW, Yao J, Harris G, Chapman KT: Glucose-lowering in a db/db mouse model by dihydropyridine diacid glycogen phosphorylase inhibitors. Bioorg Med Chem Lett (2003) 13(20):3405-3408. • Structural requirements for efficient inhibition by dihydropyridine diacid derivatives.
41. Chen J, Liu J, Zhang L, Wu G, Hua W, Wu X, Sun H: Pentacyclic triterpenes. Part 3: Synthesis and biological evaluation of oleanolic acid derivatives as novel inhibitors of glycogen phosphorylase. Bioorg Med Chem Lett (2006) 16(11):2915-2919.
42. Wen X, Xia J, Cheng K, Zhang L, Zhang P, Liu J, Zhang L, Ni P, Sun H: Pentacyclic triterpenes. Part 5: Synthesis and SAR study of corosolic acid derivatives as inhibitors of glycogen phosphorylases. Bioorg Med Chem Lett (2007) 17(21):5777-5782.
43. Furukawa S, Tsurumi Y, Murakami K, Nakanishi T, Ohsumi K, Hashimoto M, Nishikawa M, Takase S, Nakayama O, Hino M: FR258900, a novel glycogen phosphorylase inhibitor isolated from Fungus No 138354 Taxonomy, fermentation, isolation and biological activities. J Antibiot (2005) 58(8):497-502. • This paper describes an unprecedented structure, a potential new lead for the GP inhibitor design.
44. Tiraidis C, Alexacou KM, Zographos SE, Leonidas DD, Gimisis T, Oikonomakos NG: FR258900, a potential anti-hyperglycemic drug, binds at the allosteric site of glycogen phosphorylase. Protein Sci (2007) 16(8):1773-1782.
45. Whittamore PR, Addie MS, Bennett SN, Birch AM, Butters M, Godfrey L, Kenny PW, Morley AD, Murray PM, Oikonomakos NG, Otterbein LR et al: Novel thienopyrrole glycogen phosphorylase inhibitors: Synthesis, in vitro SAR and crystallographic studies. Bioorg Med Chem Lett (2006) 16(21):5567-5571. • Introduction of thienopyrrole scaffolds for the replacement of indol in new allosteric site inhibitors.
46. Rosauer KG, Ogawa AK, Willoughby CA, Ellsworth KP, Geissler WM, Myers RW, Deng Q, Chapman KT, Harris G, Moller DE: Novel 3,4-dihydroquinolin-2(1H)-one inhibitors of human glycogen phosphorylase a. Bioorg Med Chem Lett (2003) 13(24):4385-4388. • First use of dihydroquinolone type indolcarboxamides, SAR for the indol moiety.
47. Birch AM, Kenny PW, Oikonomakos NG, Otterbein L, Schofield P, Whittamore PR, Whalley DP: Development of potent, orally active 1-substituted-3,4- dihydro-2-quinolone glycogen phosphorylase inhibitors. Bioorg Med Chem Lett (2007) 17(2):394-399. • Combination of thienopyrroles and dihydroquinolones.
48. Wright SW, Rath VL, Genereux PE, Hageman DL, Levy CB, McClure LD, McCoid SC, McPherson RK, Schelhorn TM, Wilder DE, Zavadoski WJ et al: 5-Chloroindoloyl glycine amide inhibitors of glycogen phosphorylase: Synthesis, in vitro, in vivo, and X-ray crystallographic characterization. Bioorg Med Chem Lett (2005) 15(2):459-465. • Simplified 5-chloroindolcarboxamide inhibitors with nanomolar cellular activity.
49. Dudash J Jr, Zhang Y, Moore JB, Look R, Liang Y, Beavers MP, Conway BR, Rybczynski PJ, Demarest KT: Synthesis and evaluation of 3-anilino- quinoxalinones as glycogen phosphorylase inhibitors. Bioorg Med Chem Lett (2005) 15(21):4790-4793.
50. Li YH, Coppo FT, Evans KA, Graybill TL, Patel M, Gale J, Li H, Tavares F, Thomson SA: Synthesis and structure-activity relationships of 3-phenyl-2-propenamides as inhibitors of glycogen phosphorylase a. Bioorg Med Chem Lett (2006) 16(22):5892-5896.
51. Jakobs S, Fridrich D, Hofem S, Pahlke G, Eisenbrand G: Natural flavonoids are potent inhibitors of glycogen phosphorylase. Mol Nutr Food Res (2006) 50(1):52-57.
52. Juhász L, Docsa T, Brunyászki A, Gergely P, Antus S: Synthesis and glycogen phosphorylase inhibitor activity of 2,3-dihydrobenzo[1,4]dioxin derivatives. Bioorg Med Chem (2007) 15(12):4048-4056.
53. Chen L, Li H, Liu J, Zhang L, Liu H, Jiang H: Discovering benzamide derivatives as glycogen phosphorylase inhibitors and their binding site at the enzyme. Bioorg Med Chem (2007) 15(21):6763-6774.
54. Potterton L, McNicholas S, Krissinel E, Gruber J, Cowtan K, Emsley P, Murshudov GN, Cohen S, Perrakis A, Noble M: Developments in the CCP4 molecular-graphics project. Acta Crystallogr (2004) 60(Pt 12 Pt 1):2288-2294.