Phytogenic polyphenols as glycogen phosphorylase inhibitors: The potential of triterpenes and flavonoids for glycaemic control in type 2 diabetes

Current Medicinal Chemistry

Volumn 24, Issue 4, 2017, Pages 384-403

  Stravodimos, George A ^a   Chetter, Ben A ^b   Kyriakis, Efthimios ^a   Kantsadi, Anastassia L ^a   Chatzileontiadou, Demetra S M ^a   Skamnaki, Vassiliki T ^a   Kato, Atsushi ^c   Hayes, Joseph M ^b   Leonidas, Demetres D ^a  

^a UNIVERSITY OF THESSALY   (Greece)

^b UNIVERSITY OF CENTRAL LANCASHIRE   (United Kingdom)

^c UNIVERSITY OF TOYAMA   (Japan)

Author keywords

Alpha glucosidases; Antioxidants; Diabetes; Flavonoids; Glycogen phosphorylase; Pentacyclic triterpenes

Indexed keywords

ALPHA GLUCOSIDASE INHIBITOR; ANTIDIABETIC AGENT; ANTIOXIDANT; FLAVONOID; GLYCOGEN PHOSPHORYLASE; GLYCOSYLTRANSFERASE INHIBITOR; POLYPHENOL DERIVATIVE; QUERCETIN; TERPENOID DERIVATIVE; TRITERPENE DERIVATIVE; ENZYME INHIBITOR; GLUCOSE BLOOD LEVEL; POLYPHENOL; TRITERPENE;

ALLOSTERISM; ANTIDIABETIC ACTIVITY; ANTIOXIDANT ACTIVITY; BINDING AFFINITY; DRUG BINDING SITE; DRUG CONFORMATION; DRUG DESIGN; DRUG EFFECT; DRUG POTENCY; DRUG STRUCTURE; GLYCEMIC CONTROL; HUMAN; LIGAND BINDING; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PROTEIN INTERACTION; PROTEIN LIGAND INTERACTION; PROTEIN STRUCTURE; REVIEW; TEA; X RAY CRYSTALLOGRAPHY; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; CHEMISTRY; DIABETES MELLITUS, TYPE 2; GLUCOSE BLOOD LEVEL; METABOLISM;

ANIMALS; BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; ENZYME INHIBITORS; GLYCOGEN PHOSPHORYLASE; HUMANS; POLYPHENOLS; TRITERPENES;

EID: 85016162210     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867324666161118122534     Document Type: Review

References (120)

1. Zimmet, P.Z.; Magliano, D.J.; Herman, W.H.; Shaw, J.E. Diabetes: a 21st century challenge. Lancet Diabetes Endocrinol., 2014, 2(1), 56-64.
2. Pasupuleti, V.K.; Anderson, J.W. Nutraceuticals, glycemic health and type 2 diabetes. 1st ed. Wiley-Blackwell: Oxford, 2008.
3. Hayes, J.M.; Kantsadi, A.L.; Leonidas, D.D. Natural products and their derivatives as inhibitors of glycogen phosphorylase: potential treatment for type 2 diabetes. Phytochem. Rev., 2014, 13(2), 471-498.
4. Hellerstein, M.K.; Neese, R.A.; Linfoot, P.; Christiansen, M.; Turner, S.; Letscher, A. Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study. J. Clin. Invest., 1997, 100(5), 1305-1319.
5. Wagman, A.S.; Nuss, J.M. Current therapies and emerging targets for the treatment of diabetes. Curr. Pharm. Des., 2001, 7(6), 417-450.
6. Somsak, L.; Czifrak, K.; Toth, M.; Bokor, E.; Chrysina, E.D.; Alexacou, K.M.; Hayes, J.M.; Tiraidis, C.; Lazoura, E.; Leonidas, D.D.; Zographos, S.E.; Oikonomakos, N.G. New inhibitors of glycogen phosphorylase as potential antidiabetic agents. Curr. Med. Chem., 2008, 15(28), 2933-2983.
7. Oikonomakos, N.G. Glycogen phosphorylase as a molecular target for type 2 diabetes therapy. Curr. Protein. Pept. Sci., 2002, 3(6), 561-586.
8. Treadway, J.L.; Mendys, P.; Hoover, D.J. Glycogen phosphorylase inhibitors for treatment of type 2 diabetes mellitus. Expert Opin. Investig. Drugs, 2001, 10(3), 439-454.
9. Agius, L. Physiological control of liver glycogen metabolism: lessons from novel glycogen phosphorylase inhibitors. Mini Rev. Med. Chem., 2010, 10(12), 1175-1187.
10. Furukawa, S.; Murakami, K.; Nishikawa, M.; Nakayama, O.; Hino, M. FR258900, a novel glycogen phosphorylase inhibitor isolated from Fungus No. 138354. II. Antihyperglycemic effects in diabetic animal models. J. Antibiot. (Tokyo), 2005, 58(8), 503-506.
11. Hoover, D.J.; Lefkowitz-Snow, S.; Burgess-Henry, J.L.; Martin, W.H.; Armento, S.J.; Stock, I.A.; McPherson, R.K.; Genereux, P.E.; Gibbs, E.M.; Treadway, J.L. Indole-2-carboxamide inhibitors of human liver glycogen phosphorylase. J.Med. Chem., 1998, 41, 2934-2938.
12. Martin, W.H.; Hoover, D.J.; Armento, S.J.; Stock, I.A.; McPherson, R.K.; Danley, D.E.; Stevenson, R.W.; Barrett, E.J.; Treadway, J.L. Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo. Proc. Natl. Acad. Sci. USA, 1998, 95, 1776-1781.
13. Docsa, T.; Czifrak, K.; Huse, C.; Somsak, L.; Gergely, P. Effect of glucopyranosylidene-spiro-thiohydantoin on glycogen metabolism in liver tissues of streptozotocin-induced and obese diabetic rats. Mol. Med. Report., 2011, 4(3), 477-481.
14. Nagy, L.; Docsa, T.; Szanto, M.; Brunyanszki, A.; Hegedus, C.; Marton, J.; Konya, B.; Virag, L.; Somsak, L.; Gergely, P.; Bai, P. Glycogen phosphorylase inhibitor N-(3,5-dimethyl-benzoyl)-N '-(beta-D-glucopyranosyl)urea improves glucose tolerance under normoglycemic and diabetic conditions and rearranges hepatic metabolism. PLoS One, 2013, 8(7), e69420.
15. Docsa, T.; Marics, B.; Nemeth, J.; Huse, C.; Somsak, L.; Gergely, P.; Peitl, B. Insulin sensitivity is modified by a glycogen phosphorylase inhibitor: glucopyranosylidenespiro-thiohydantoin in streptozotocin-induced diabetic rats. Curr. Top. Med. Chem., 2015, 15(23), 2390-2394.
16. Goyard, D.; Konya, B.; Chajistamatiou, A.S.; Chrysina, E.D.; Leroy, J.; Balzarin, S.; Tournier, M.; Tousch, D.; Petit, P.; Duret, C.; Maurel, P.; Somsak, L.; Docsa, T.; Gergely, P.; Praly, J.P.; Azay-Milhau, J.; Vidal, S. Glucosederived spiro-isoxazolines are anti-hyperglycemic agents against type 2 diabetes through glycogen phosphorylase inhibition. Eur. J. Med. Chem., 2016, 108, 444-454.
17. Oikonomakos, N.G.; Somsak, L. Advances in glycogen phosphorylase inhibitor design. Curr. Opin. Invest. Drugs, 2008, 9(4), 379-395.
18. Somsak, L. Glucose derived inhibitors of glycogen phosphorylase. C.R. Chim., 2011, 14(2-3), 211-223.
19. Bokor, E.; Szennyes, E.; Csupasz, T.; Toth, N.; Docsa, T.; Gergely, P.; Somsak, L. C-(2-Deoxy-d-arabino-hex-1-enopyranosyl)-oxadiazoles: synthesis of possible isomers and their evaluation as glycogen phosphorylase inhibitors. Carbohydr. Res., 2015, 412, 71-79.
20. Begum, J.; Varga, G.; Docsa, T.; Gergely, P.; Hayes, J.M.; Juhasz, L.; Somsak, L. Computationally motivated synthesis and enzyme kinetic evaluation of N-([small beta]-dglucopyranosyl)-1,2,4-triazolecarboxamides as glycogen phosphorylase inhibitors. Med. Chem. Comm., 2015, 6(1), 80-89.
21. Kun, S.; Bokor, E.; Varga, G.; Szocs, B.; Pahi, A.; Czifrak, K.; Toth, M.; Juhasz, L.; Docsa, T.; Gergely, P.; Somsak, L. New synthesis of 3-(beta-D-glucopyranosyl)-5-substituted-1,2,4-triazoles, nanomolar inhibitors of glycogen phosphorylase. Eur. J. Med. Chem., 2014, 76, 567-579.
22. Czifrak, K.; Pahi, A.; Deak, S.; Kiss-Szikszai, A.; Kover, K.E.; Docsa, T.; Gergely, P.; Alexacou, K.M.; Papakonstantinou, M.; Leonidas, D.D.; Zographos, S.E.; Chrysina, E.D.; Somsak, L. Glucopyranosylidene-spiro-iminothiazolidinone, a new bicyclic ring system: synthesis, derivatization, and evaluation for inhibition of glycogen phosphorylase by enzyme kinetic and crystallographic methods. Bioorg. Med. Chem., 2014, 22(15), 4028-4041.
23. Polyak, M.; Varga, G.; Szilagyi, B.; Juhasz, L.; Docsa, T.; Gergely, P.; Begum, J.; Hayes, J.M.; Somsak, L. Synthesis, enzyme kinetics and computational evaluation of N-(beta-D-glucopyranosyl) oxadiazolecarboxamides as glycogen phosphorylase inhibitors. Biorg. Med. Chem., 2013, 21(18), 5738-5747.
24. Bokor, E.; Szilagyi, E.; Docsa, T.; Gergely, P.; Somsak, L. Synthesis of substituted 2-(beta-D-glucopyranosyl)-benzimidazoles and their evaluation as inhibitors of glycogen phosphorylase. Carbohydr. Res., 2013, 381, 179-186.
25. Bokor, E.; Docsa, T.; Gergely, P.; Somsak, L. CGlucopyranosyl-1,2,4-triazoles as new potent inhibitors of glycogen phosphorylase. ACS Med. Chem. Lett., 2013, 4(7), 47-50.
26. Nagy, V.; Felfoldi, N.; Konya, B.; Praly, J.P.; Docsa, T.; Gergely, P.; Chrysina, E.D.; Tiraidis, C.; Kosmopoulou, M.N.; Alexacou, K.M.; Konstantakaki, M.; Leonidas, D.D.; Zographos, S.E.; Oikonomakos, N.G.; Kozmon, S.; Tvaroska, I.; Somsak, L. N-(4-Substituted-benzoyl)-N '-(beta-D-glucopyranosyl)ureas as inhibitors of glycogen phosphorylase: Synthesis and evaluation by kinetic, crystallographic, and molecular modelling methods. Biorg. Med. Chem., 2012, 20(5), 1801-1816.
27. Konya, B.; Docsa, T.; Gergely, P.; Somsak, L. Synthesis of heterocyclic N-(beta-D-glucopyranosyl)carboxamides for inhibition of glycogen phosphorylase. Carbohydr. Res., 2012, 351, 56-63.
28. Parmenopoulou, V.; Kantsadi, A.L.; Tsirkone, V.G.; Chatzileontiadou, D.S.; Manta, S.; Zographos, S.E.; Molfeta, C.; Archontis, G.; Agius, L.; Hayes, J.M.; Leonidas, D.D.; Komiotis, D. Structure based inhibitor design targeting glycogen phosphorylase b. Virtual screening, synthesis, biochemical and biological assessment of novel N-acyl-beta-dglucopyranosylamines. Bioorg. Med. Chem., 2014, 22(17), 4810-4825.
29. Varga, G.; Docsa, T.; Gergely, P.; Juhasz, L.; Somsak, L. Synthesis of tartaric acid analogues of FR258900 and their evaluation as glycogen phosphorylase inhibitors. Bioorg. Med. Chem. Lett., 2013, 23(6), 1789-1792.
30. Szocs, B.; Toth, M.; Docsa, T.; Gergely, P.; Somsak, L. Synthesis of 2-(beta-D-glucopyranosyl)-5-(substitutedamino)-1,3,4-oxa-and-thiadiazoles for the inhibition of glycogen phosphorylase. Carbohydr. Res., 2013, 381, 187-195.
31. Toth, M.; Szocs, B.; Kaszas, T.; Docsa, T.; Gergely, P.; Somsak, L. Synthesis of 2-(beta-D-glucopyranosylamino)-5-substituted-1,3,4-oxadiazoles for inhibition of glycogen phosphorylase. Carbohydr. Res., 2013, 381, 196-204.
32. Goyard, D.; Baron, M.; Skourti, P.V.; Chajistamatiou, A.S.; Docsa, T.; Gergely, P.; Chrysina, E.D.; Praly, J.P.; Vidal, S. Synthesis of 1,2,3-triazoles from xylosyl and 5-thioxylosyl azides: evaluation of the xylose scaffold for the design of potential glycogen phosphorylase inhibitors. Carbohydr. Res., 2012, 364, 28-40.
33. Feuillastre, S.; Chajistamatiou, A.S.; Potamitis, C.; Zervou, M.; Zoumpoulakis, P.; Chrysina, E.D.; Praly, J.P.; Vidal, S. C-Glucosylated malonitrile as a key intermediate towards carbohydrate-based glycogen phosphorylase inhibitors. Bioorg. Med. Chem., 2012, 20(18), 5592-5599.
34. Somsak, L.; Bokor, E.; Czibere, B.; Czifrak, K.; Koppany, C.; Kulcsar, L.; Kun, S.; Szilagyi, E.; Toth, M.; Docsa, T.; Gergely, P. Synthesis of C-xylopyranosyl and xylopyranosylidene-spiro-heterocycles as potential inhibitors of glycogen phosphorylase. Carbohydr. Res., 2014, 399, 38-48.
35. Juhasz, L.; Varga, G.; Sztankovics, A.; Beke, F.; Docsa, T.; Kiss-Szikszai, A.; Gergely, P.; Kona, J.; Tvaroška, I.; Somsak, L. Structure-activity relationships of glycogen phosphorylase inhibitor FR258900 and its analogues: a combined synthetic, enzyme kinetics, and computational study. Chem. Plus Chem., 2014, 79(11), 1558-1568.
36. Bokor, E.; Kun, S.; Docsa, T.; Gergely, P.; Somsak, L. 4(5)-Aryl-2°C-glucopyranosyl-imidazoles as new nanomolar glucose analogue inhibitors of glycogen phosphorylase. ACS Med. Chem. Lett., 2015, 6(12), 1215-1219.
37. Donnier-Marechal, M.; Goyard, D.; Folliard, V.; Docsa, T.; Gergely, P.; Praly, J.P.; Vidal, S. 3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors. Beilstein J. Org. Chem., 2015, 11, 499-503.
38. Goyard, D.; Docsa, T.; Gergely, P.; Praly, J.P.; Vidal, S. Synthesis of 4-amidomethyl-1-glucosyl-1,2,3-triazoles and evaluation as glycogen phosphorylase inhibitors. Carbohydr. Res., 2015, 402, 245-251.
39. Bokor, E.; Szeles, Z.; Docsa, T.; Gergely, P.; Somsak, L. CGlucopyranosyl-1,2,4-triazol-5-ones: synthesis and inhibition of glycogen phosphorylase. Carbohydr. Res., 2016, 429, 128-134.
40. Donnier-Marechal, M.; Vidal, S. Glycogen phosphorylase inhibitors: a patent review (2013-2015). Expert Opin. Ther. Pat., 2016, 26(2), 199-212.
41. Gershenzon, J.; Dudareva, N. The function of terpene natural products in the natural world. Nat. Chem. Biol., 2007, 3(7), 408-414.
42. Nazaruk, J.; Borzym-Kluczyk, M. The role of triterpenes in the management of diabetes mellitus and its complications. Phytochem. Rev., 2015, 14(4), 675-690.
43. Sheng, H.; Sun, H. Synthesis, biology and clinical significance of pentacyclic triterpenes: a multi-target approach to prevention and treatment of metabolic and vascular diseases. Nat. Prod. Rep., 2011, 28(3), 543-593.
44. Wen, X.; Sun, H.; Liu, J.; Wu, G.; Zhang, L.; Wu, X.; Ni, P. Pentacyclic triterpenes. Part 1: the first examples of naturally occurring pentacyclic triterpenes as a new class of inhibitors of glycogen phosphorylases. Bioorg. Med. Chem. Lett., 2005, 15(22), 4944-4948.
45. Fukushima, M.; Matsuyama, F.; Ueda, N.; Egawa, K.; Takemoto, J.; Kajimoto, Y.; Yonaha, N.; Miura, T.; Kaneko, T.; Nishi, Y.; Mitsui, R.; Fujita, Y.; Yamada, Y.; Seino, Y. Effect of corosolic acid on postchallenge plasma glucose levels. Diabetes Res. Clin. Pract., 2006, 73(2), 174-177.
46. Miura, T.; Ueda, N.; Yamada, K.; Fukushima, M.; Ishida, T.; Kaneko, T.; Matsuyama, F.; Seino, Y. Antidiabetic effects of corosolic acid in KK-Ay diabetic mice. Biol. Pharm. Bull., 2006, 29(3), 585-587.
47. 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.
48. Wen, X.; Sun, H.; Liu, J.; Cheng, K.; Zhang, P.; Zhang, L.; Hao, J.; Ni, P.; Zographos, S.E.; Leonidas, D.D.; Alexacou, K.M.; Gimisis, T.; Hayes, J.M.; Oikonomakos, N.G. Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: synthesis, structure-activity relationships, and X-ray crystallographic studies. J. Med. Chem., 2008, 51(12), 3540-3554.
49. Liang, Z.; Zhang, L.; Li, L.; Liu, J.; Li, H.; Chen, L.; Cheng, K.; Zheng, M.; Wen, X.; Zhang, P.; Hao, J.; Gong, Y.; Zhang, X.; Zhu, X.; Chen, J.; Liu, H.; Jiang, H.; Luo, C.; Sun, H. Identification of pentacyclic triterpenes derivatives as potent inhibitors against glycogen phosphorylase based on 3D-QSAR studies. Eur. J. Med. Chem., 2011, 46(6), 2011-2021.
50. Chen, J.; Gong, Y.C.; Liu, J.; Hua, W.Y.; Zhang, L.Y.; Sun, H.B. Synthesis and biological evaluation of novel pyrazolo[ 4,3-b]oleanane derivatives as inhibitors of glycogen phosphorylase. Chem. Biodivers., 2008, 5(7), 1304-1312.
51. Cheng, K.; Liu, J.; Liu, X.; Li, H.; Sun, H.; Xie, J. Synthesis of glucoconjugates of oleanolic acid as inhibitors of glycogen phosphorylase. Carbohydr. Res., 2009, 344(7), 841-850.
52. Cheng, K.G.; Liu, J.; Sun, H.B.; Bokor, E.; Czifrak, K.; Konya, B.; Toth, M.; Docsa, T.; Gergely, P.; Somsak, L. Tethered derivatives of D-glucose and pentacyclic triterpenes for homo/heterobivalent inhibition of glycogen phosphorylase. New J. Chem., 2010, 34(7), 1450-1464.
53. Hao, J.; Zhang, P.; Wen, X.A.; Sun, H.B. Efficient access to 2-isobetulinic acid, 2-isooleanolic acid, and 2-isoursolic acid. J. Org. Chem., 2008, 73(18), 7405-7408.
54. Wen, X.; Xia, J.; Cheng, K.; Zhang, L.; Zhang, P.; Liu, J.; 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.
55. Wen, X.; Zhang, P.; Liu, J.; Zhang, L.; Wu, X.; Ni, P.; Sun, H. Pentacyclic triterpenes. Part 2: Synthesis and biological evaluation of maslinic acid derivatives as glycogen phosphorylase inhibitors. Bioorg. Med. Chem. Lett., 2006, 16(3), 722-726.
56. Zhang, P.; Hao, J.; Liu, J.; Lu, Q.; Sheng, H.M.; Zhang, L.Y.; Sun, H.B. Synthesis of 3-deoxypentacyclic triterpene derivatives as inhibitors of glycogen phosphorylase. J. Nat. Prod., 2009, 72(8), 1414-1418.
57. Zhang, L.; Chen, J.; Gong, Y.; Liu, J.; Zhang, L.; Hua, W.; Sun, H. Synthesis and biological evaluation of asiatic acid derivatives as inhibitors of glycogen phosphorylases. Chem. Biodivers., 2009, 6(6), 864-874.
58. Zhang, L.; Dong, J.; Liu, J.; Zhang, L.; Kong, L.; Yao, H.; Sun, H. Synthesis and biological evaluation of novel pentacyclic triterpene derivatives as potential PPARgamma agonists. Med. Chem., 2013, 9(1), 118-125.
59. Luo, J.G.; Liu, J.; Kong, L.Y. New pentacyclic triterpenes from Gypsophila oldhamiana and their biological evaluation as glycogen phosphorylase inhibitors. Chem. Biodivers., 2008, 5(5), 751-757.
60. Yang, J.; Chen, H.; Zhang, L.; Wang, Q.; Lai, M.X. Antidiabetic effect of standardized extract of potentilla discolor bunge and identification of its active components. Drug Dev. Res., 2010, 71(2), 127-132.
61. Ong, K.C.; Khoo, H.E. Effects of myricetin on glycemia and glycogen metabolism in diabetic rats. Life Sci., 2000, 67(14), 1695-1705.
62. Ahmad, M.; Akhtar, M.S.; Malik, T.; Gilani, A.H. Hypoglycaemic action of the flavonoid fraction of Cuminum nigrum seeds. Phytother. Res., 2000, 14(2), 103-106.
63. Anila, L.; Vijayalakshmi, N.R. Beneficial effects of flavonoids from Sesamum indicum, Emblica officinalis and Momordica charantia. Phytother. Res., 2000, 14(8), 592-595.
64. Middleton, E., Jr.; Kandaswami, C.; Theoharides, T.C. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol. Rev., 2000, 52(4), 673-751.
65. Nijveldt, R.J.; van Nood, E.; van Hoorn, D.E.C.; Boelens, P.G.; van Norren, K.; van Leeuwen, P.A.M. Flavonoids: a review of probable mechanisms of action and potential applications. Am. J. Clin. Nutr., 2001, 74(4), 418-425.
66. Rimm, E.B.; Katan, M.B.; Ascherio, A.; Stampfer, M.J.; Willett, W.C. Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann. Intern. Med., 1996, 125(5), 384-389.
67. Rossi, M.; Negri, E.; Talamini, R.; Bosetti, C.; Parpinel, M.; Gnagnarella, P.; Franceschi, S.; Dal Maso, L.; Montella, M.; Giacosa, A.; La Vecchia, C. Flavonoids and colorectal cancer in Italy. Cancer Epidemiol. Biomarkers Prev., 2006, 15(8), 1555-1558.
68. Scalbert, A.; Williamson, G. Dietary intake and bioavailability of polyphenols. J. Nutr., 2000, 130(8), 2073s-2085s.
69. Kinoshita, T.; Lepp, Z.; Chuman, H. Construction of a novel database for flavonoids. J. Med. Invest., 2005, 52, 291-292.
70. Peterson, J.; Dwyer, J. An informatics approach to flavonoid database development. J. Food Compos. Anal., 2000, 13, 441-454.
71. Beecher, G.R. Overview of dietary flavonoids: nomenclature, occurrence and intake. J. Nutr., 2003, 133(10), 3248S-3254S.
72. Cao, J.; Chen, W.; Zhang, Y.; Zhang, Y.Q.; Zhao, X.J. Content of selected flavonoids in 100 edible vegetables and fruits. Food Sci. Technol. Res., 2010, 16(5), 395-402.
73. Kantsadi, A.L.; Apostolou, A.; Theofanous, S.; Stravodimos, G.A.; Kyriakis, E.; Gorgogietas, V.A.; Chatzileontiadou, D.S.; Pegiou, K.; Skamnaki, V.T.; Stagos, D.; Kouretas, D.; Psarra, A.M.; Haroutounian, S.A.; Leonidas, D.D. Biochemical and biological assessment of the inhibitory potency of extracts from vinification byproducts of Vitis vinifera extracts against glycogen phosphorylase. Food Chem. Toxicol., 2014, 67, 35-43.
74. Kamiyama, O.; Sanae, F.; Ikeda, K.; Higashi, Y.; Minami, Y.; Asano, N.; Adachi, I.; Kato, A. In vitro inhibition of α-glucosidases and glycogen phosphorylase by catechin gallates in green tea. Food Chem., 2010, 122(4), 1061-1066.
75. Kato, A.; Minoshima, Y.; Yamamoto, J.; Adachi, I.; Watson, A.A.; Nash, R.J. Protective effects of dietary chamomile tea on diabetic complications. J. Agric. Food. Chem., 2008, 56, (17), 8206-8211.
76. Irwin, J.J.; Sterling, T.; Mysinger, M.M.; Bolstad, E.S.; Coleman, R.G. ZINC: A free tool to discover chemistry for biology. J. Chem. Inf. Model., 2012, 52(7), 1757-1768.
77. 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.
78. Kato, A.; Nasu, N.; Takebayashi, K.; Adachi, I.; Minami, Y.; Sanae, F.; Asano, N.; Watson, A.A.; Nash, R.J. Structure-activity relationships of flavonoids as potential inhibitors of glycogen phosphorylase. J. Agric. Food. Chem., 2008, 56(12), 4469-4473.
79. Oikonomakos, N.G.; Schnier, J.B.; Zographos, S.E.; Skamnaki, V.T.; Tsitsanou, K.E.; Johnson, L.N. Flavopiridol inhibits glycogen phosphorylase by binding at the inhibitor site. J. Biol. Chem., 2000, 275(44), 34566-34573.
80. Tsitsanou, K.E.; Hayes, J.M.; Keramioti, M.; Mamais, M.; Oikonomakos, N.G.; Kato, A.; Leonidas, D.D.; Zographos, S.E. Sourcing the affinity of flavonoids for the glycogen phosphorylase inhibitor site via crystallography, kinetics and QM/MM-PBSA binding studies: Comparison of chrysin and flavopiridol. Food Chem. Toxicol., 2013, 61, 14-27.
81. Kyriakis, E.; Stravodimos, G.A.; Kantsadi, A.L.; Chatzileontiadou, D.S.; Skamnaki, V.T.; Leonidas, D.D. Natural flavonoids as antidiabetic agents. The binding of gallic and ellagic acids to glycogen phosphorylase b. FEBS Lett., 2015, 589(15), 1787-1794.
82. Papageorgiou, A.C.; Oikonomakos, N.G.; Leonidas, D.D. Inhibition of rabbit muscle glycogen phosphorylase by D-gluconohydroximo-1,5-lactone-N-phenylurethane. Arch. Biochem. Biophys., 1989, 272(2), 376-385.
83. Kasvinsky, P.J.; Madsen, N.B.; Sygusch, J.; Fletterick, R.J. Regulation of glycogen phosphorylase - a by nucleotide derivatives-kinetic and x-ray crystallographic studies. J. Biol. Chem., 1978, 253(9), 3343-3351.
84. Madsen, N.B.; Shechosky, S.; Fletterick, R.J. Site-site interactions in glycogen phosphorylase b probed by ligands specific for each site. Biochemistry, 1983, 22(19), 4460-4465.
85. Kosmopoulou, M.N.; Leonidas, D.D.; Chrysina, E.D.; Bischler, N.; Eisenbrand, G.; Sakarellos, C.E.; Pauptit, R.; Oikonomakos, N.G. 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.
86. Kosmopoulou, M.N.; Leonidas, D.D.; Chrysina, E.D.; Eisenbrand, G.; Oikonomakos, N.G. Indirubin-3 '-aminooxyacetate 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.
87. Oikonomakos, N.G.; Kosmopoulou, M.N.; Leonidas, D.D.; Chrysina, E.D.; Tiraidis, C.; Bischler, N.; Tsitsanou, K.E.; Zographos, S.E.; Kostas, I.D.; Eisenbrand, G. In Indirubin, the Red Shade of Indigo. Meijer, L.; Guyard, N.; Skaltsounis, L.; Eisenbrand, G., Eds.; Life in Progress Editions: Roscoff, France, 2006, pp. 177-189.
88. Hampson, L.J.; Arden, C.; Agius, L.; Ganotidis, M.; Kosmopoulou, M.N.; Tiraidis, C.; Elemes, Y.; Sakarellos, C.; Leonidas, D.D.; Oikonomakos, N.G. Bioactivity of glycogen phosphorylase inhibitors that bind to the purine nucleoside site. Bioorg. Med. Chem., 2006, 14(23), 7835-7845.
89. Wilcken, R.; Zimmermann, M.O.; Lange, A.; Joerger, A.C.; Boeckler, F.M. Principles and applications of halogen bonding in medicinal chemistry and chemical biology. J. Med. Chem., 2013, 56(4), 1363-1388.
90. Kantsadi, A.L.; Hayes, J.M.; Manta, S.; Skamnaki, V.T.; Kiritsis, C.; Psarra, A.M.G.; Koutsogiannis, Z.; Dimopoulou, A.; Theofanous, S.; Nikoleousakos, N.; Zoumpoulakis, P.; Kontou, M.; Papadopoulos, G.; Zographos, S.E.; Komiotis, D.; Leonidas, D.D. The s-hole phenomenon of halogen atoms forms the structural basis of the strong inhibitory potency of C5 halogen substituted glucopyranosyl nucleosides towards glycogen phosphorylase b. Chem. Med. Chem., 2012, 7(4), 722-732.
91. Ernst, B.; Magnani, J.L. From carbohydrate leads to glycomimetic drugs. Nat. Rev. Drug Discov., 2009, 8(8), 661-677.
92. Somsak, L.; Bokor, E.; Czifrak, K.; Juhasz, L.; Toth, M. In Topics in the Prevention, Treatment and Complications of Type 2 Diabetes. Zimering, M., Ed.; InTech, 2011.
93. Valko, M.; Izakovic, M.; Mazur, M.; Rhodes, C.J.; Telser, J. Role of oxygen radicals in DNA damage and cancer incidence. Mol. Cell. Biochem., 2004, 266(1-2), 37-56.
94. Schoonover, L.L. Oxidative stress and the role of antioxidants in cardiovascular risk reduction. Prog. Cardiovasc. Nurs., 2001, 16(1), 30-32.
95. Halliwell, B. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet, 1994, 344(8924), 721-724.
96. Baynes, J.W. Role of oxidative stress in development of complications in diabetes. Diabetes, 1991, 40(4), 405-412.
97. Wolff, S.P. Diabetes mellitus and free radicals. Free radicals, transition metals and oxidative stress in the aetiology of diabetes mellitus and complications. Br. Med. Bull., 1993, 49(3), 642-652.
98. Rani, V.; Deep, G.; Singh, R.K.; Palle, K.; Yadav, U.C. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies. Life Sci., 2016, 148, 183-193.
99. Giugliano, D.; Ceriello, A.; Paolisso, G. Oxidative stress and diabetic vascular complications. Diabetes Care, 1996, 19(3), 257-267.
100. Nishikawa, T.; Edelstein, D.; Du, X.L.; Yamagishi, S.; Matsumura, T.; Kaneda, Y.; Yorek, M.A.; Beebe, D.; Oates, P.J.; Hammes, H.P.; Giardino, I.; Brownlee, M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature, 2000, 404(6779), 787-790.
101. Singh, D.K.; Winocour, P.; Farrington, K. Oxidative stress in early diabetic nephropathy: fueling the fire. Nat. Rev. Endocrinol., 2011, 7(3), 176-184.
102. Giacco, F.; Brownlee, M. Oxidative stress and diabetic complications. Circ. Res., 2010, 107(9), 1058-1070.
103. Rochette, L.; Zeller, M.; Cottin, Y.; Vergely, C. Diabetes, oxidative stress and therapeutic strategies. Biochim. Biophys. Acta, 2014, 1840(9), 2709-2729.
104. Takac, I.; Schroder, K.; Zhang, L.; Lardy, B.; Anilkumar, N.; Lambeth, J.D.; Shah, A.M.; Morel, F.; Brandes, R.P. The E-loop is involved in hydrogen peroxide formation by the NADPH oxidase Nox4. J. Biol. Chem., 2011, 286(15), 13304-13313.
105. Wolff, S.P.; Crabbe, M.J.C.; Thornalley, P.J. The autooxidation of simple monosaccharides. Experientia, 1984, 40(244-246).
106. Wolff, S.P.; Jiang, Z.Y.; Hunt, J.V. Protein glycation and oxidative stress in diabetes mellitus and ageing. Free Radic. Biol. Med., 1991, 10(5), 339-352.
107. Yan, S.D.; Schmidt, A.M.; Anderson, G.M.; Zhang, J.; Brett, J.; Zou, Y.S.; Pinsky, D.; Stern, D. Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J. Biol. Chem., 1994, 269(13), 9889-9897.
108. Maziere, C.; Auclair, M.; Rose-Robert, F.; Leflon, P.; Maziere, J.C. Glucose-enriched medium enhances cell-mediated low density lipoprotein peroxidation. FEBS Lett., 1995, 363(3), 277-279.
109. Burda, S.; Oleszek, W. Antioxidant and antiradical activities of flavonoids. J. Agric. Food. Chem., 2001, 49(6), 2774-2779.
110. Blum, S.; Vardi, M.; Brown, J.B.; Russell, A.; Milman, U.; Shapira, C.; Levy, N.S.; Miller-Lotan, R.; Asleh, R.; Levy, A.P. Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype. Pharmacogenomics, 2010, 11(5), 675-684.
111. Cameron, N.E.; Cotter, M.A.; Maxfield, E.K. Anti-oxidant treatment prevents the development of peripheral nerve dysfunction in streptozotocin-diabetic rats. Diabetologia, 1993, 36(4), 299-304.
112. Kowluru, R.A.; Zhong, Q.; Santos, J.M.; Thandampallayam, M.; Putt, D.; Gierhart, D.L. Beneficial effects of the nutritional supplements on the development of diabetic retinopathy. Nutr. Metab. (Lond.), 2014, 11(1), 8.
113. Siman, C.M.; Eriksson, U.J. Vitamin E decreases the occurrence of malformations in the offspring of diabetic rats. Diabetes, 1997, 46(6), 1054-1061.
114. Ceriello, A. New insights on oxidative stress and diabetic complications may lead to a "causal" antioxidant therapy. Diabetes Care, 2003, 26(5), 1589-1596.
115. Jovanovic, S.V.; Steenken, S.; Tosic, M.; Marjanovic, B.; Simic, M.G. Flavonoids as antioxidants. JACS, 1994, 116(11), 4846-4851.
116. Rice-Evans, C. In Antioxidant Food Supplements in Human Health. Packer, L.; Hiramatsu, M.; Yoshikawa, T., Eds.; Academic Press: San Diego, CA, 1999, pp. 239-253.
117. Bors, W.; Heller, W.; Michel, C.; Saran, M. Flavonoids as antioxidants: determination of radical-scavenging efficiencies. Methods Enzymol., 1990, 186, 343-355.
118. Bors, W.; Michel, C.; Stettmaier, K. Antioxidant effects of flavonoids. BioFactors, 1997, 6(4), 399-402.
119. Cao, G.; Sofic, E.; Prior, R.L. Antioxidant and prooxidant behavior of flavonoids: structure-activity relationships. Free Radic. Biol. Med., 1997, 22(5), 749-760.
120. Chung, H.S.; Chang, L.C.; Lee, S.K.; Shamon, L.A.; van Breemen, R.B.; Mehta, R.G.; Farnsworth, N.R.; Pezzuto, J.M.; Kinghorn, A.D. Flavonoid constituents of Chorizanthe diffusa with potential cancer chemopreventive activity. J. Agric. Food. Chem., 1999, 47(1), 36-41.