Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors from natural products: Discovery of next-generation antihyperglycemic agents

Molecules

Volumn 21, Issue 9, 2016, Pages

  Choi, Chang Ik ^a  

^a Dongguk University   (South Korea)

Author keywords

Natural product; Phlorizin; Sglt2 inhibitor; Sodium glucose cotransporter; Type 2 diabetes mellitus

Indexed keywords

ANTIDIABETIC AGENT; GLUCOSE; PHLORIZIN; SLC5A2 PROTEIN, HUMAN; SODIUM GLUCOSE COTRANSPORTER 2;

ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DIABETES MELLITUS, TYPE 2; HERBAL MEDICINE; HUMAN; METABOLISM; PHYTOTHERAPY; PROCEDURES;

ANIMALS; DIABETES MELLITUS, TYPE 2; GLUCOSE; HERBAL MEDICINE; HUMANS; HYPOGLYCEMIC AGENTS; PHLORHIZIN; PHYTOTHERAPY; SODIUM-GLUCOSE TRANSPORTER 2;

EID: 84987877197     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules21091136     Document Type: Review

References (75)

1. Baynes, J.W. Role of oxidative stress in development of complications in diabetes. Diabetes 1991, 40, 405-412.
2. International Diabetes Federation. IDF Diabetes Atlas, 7th ed.; International Diabetes Federation: Brussels, Belgium, 2015; pp. 12-14.
3. Hung, H.Y.; Qian, K.; Norris-Natschke, S.L.; Hsu, C.S.; Lee, K.H. Recent discovery of plant-derived anti-diabetic natural products. Nat. Prod. Rep. 2012, 29, 580-606.
4. Shannon, J.A.; Fisher, S. The renal tubular reabsorption of glucose in the normal dog. Am. J. Physiol. 1938, 122, 765-774.
5. Vick, H.; Diedrich, D.F.; Baumann, K. Reevaluation of renal tubular glucose transport inhibition by phlorizin analogs. Am. J. Physiol. 1973, 224, 552-557.
6. Turner, R.J.; Moran, A. Heterogeneity of sodium-dependent D-glucose transport sites along the proximal tubule: Evidence from vesicle studies. Am. J. Physiol. 1982, 242, F406-F414.
7. Hediger, M.A.; Coady, M.J.; Ikeda, T.S.; Wright, E.M. Expression cloning and cDNA sequencing of the Na+ /glucose co-transporter. Nature 1987, 330, 379-381.
8. Kanai, Y.; Lee, W.S.; You, G.; Brown, D.; Hediger, M.A. The human kidney low affinity Na+ /glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J. Clin. Investig. 1994, 93, 397-404.
9. Wright, E.M.; Loo, D.D.; Hirayama, B.A. Biology of human sodium glucose transporters. Physiol. Rev. 2011, 91, 733-794.
10. Vallon, V.; Platt, K.A.; Cunard, R.; Schroth, J.; Whaley, J.; Thomson, S.C.; Koepsell, H.; Rieg, T. SGLT2 mediates glucose reabsorption in the early proximal tubule. J. Am. Soc. Nephrol. 2011, 22, 104-112.
11. Gorboulev, V.; Schürmann, A.; Vallon, V.; Kipp, H.; Jaschke, A.; Klessen, D.; Friedrich, A.; Scherneck, S.; Rieg, T.; Cunard, R.; et al. Na+ -D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes 2012, 61, 187-196.
12. Rieg, T.; Masuda, T.; Gerasimova, M.; Mayoux, E.; Platt, K.; Powell, D.R.; Thomson, S.C.; Koepsell, H.; Vallon, V. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia. Am. J. Physiol. Renal Physiol. 2014, 306, F188-F193.
13. Farber, S.J.; Berger, E.Y.; Eaerle, D.P. Effect of diabetes and insulin on the maximum capacity of the renal tubules to reabsorb glucose. J. Clin. Investig. 1951, 30, 125-129.
14. Vestri, S.; Okamoto, M.M.; de Freitas, H.S.; Aparecida Dos Santos, R.; Nunes, M.T.; Morimatsu, M.; Heimann, J.C.; Machado, U.F. Changes in sodium or glucose filtration rate modulate expression of glucose transporters in renal proximal tubular cells of rat. J. Membr. Biol. 2001, 182, 105-112.
15. Rahmoune, H.; Thompson, P.W.; Ward, J.M.; Smith, C.D.; Hong, G.; Brown, J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 2005, 54, 3427-3434.
16. Vallon, V. The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus. Annu. Rev. Med. 2015, 66, 255-270.
17. Ehrenkranz, R.R.L.; Lewis, N.G.; Kahn, C.R.; Roth, J. Phlorizin: A review. Diabetes Metab. Res. Rev. 2005, 21, 31-38.
18. White, J.R., Jr. Apple trees to sodium glucose co-transporter inhibitors: A review of SGLT2 inhibition. Clin. Diabetes 2010, 28, 5-10.
19. Chasis, H.; Jolliffe, N.; Smith, H.W. The action of phlorizin on the excretion of glucose, xylose, sucrose, creatinine and urea by man. J. Clin. Investig. 1933, 12, 1083-1090.
20. Rossetti, L.; Smith, D.; Shulman, G.I.; Papachristou, D.; DeFronzo, R.A. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J. Clin. Investig. 1987, 79, 1510-1515.
21. Dimitrakoudis, D.; Vranic, M.; Klip, A. Effects of hyperglycemia on glucose transporters of the muscle: Use of the renal glucose reabsorption inhibitor phlorizin to control glycemia. J. Am. Soc. Nephrol. 1992, 3, 1078-1091.
22. Jonas, J.C.; Sharma, A.; Hasenkamp, W.; Ilkova, H.; Patane, G.; Laybutt, R.; Bonner-Weir, S.; Weir, G.C. Chronic hyperglycemia triggers loss of pancreatic β cell differentiation in an animal model of diabetes. J. Biol. Chem. 1999, 274, 14112-14121.
23. Abdul-Ghani, M.A.; DeFronzo, R.A. Inhibition of renal glucose absorption: A novel strategy for achieving glucose control in type 2 diabetes mellitus. Endocr. Pract. 2008, 14, 782-790.
24. Thorens, B.; Mueckler, M. Glucose transporters in the 21st century. Am. J. Physiol. Endocrinol. Metab. 2010, 298, E141-E145.
25. Bays, H. Sodium glucose co-transporter type 2 (SGLT2) inhibitors: Targeting the kidney to improve glycemic control in diabetes mellitus. Diabetes Ther. 2013, 4, 195-220.
26. Oku, A.; Ueta, K.; Arakawa, K.; Ishihara, T.; Nawano, M.; Kuronuma, Y.; Matsumoto, M.; Saito, A.; Tsujihara, K.; Anai, M.; et al. T-1095, an inhibitor of renal Na+ -glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes 1999, 48, 1794-1800.
27. Katsuno, K.; Fujimori, Y.; Takemura, Y.; Hiratochi, M.; Itoh, F.; Komatsu, Y.; Fujikura, H.; Isaji, M. Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal glucose reabsorption and modulates plasma glucose level. J. Pharmacol. Exp. Ther. 2007, 320, 323-330.
28. Fujimori, Y.; Katsuno, K.; Nakashima, I.; Ishikawa-Takemura, Y.; Fujikura, H.; Isaji, M. Remogliflozin etabonate, in a novel category of selective low-affinity sodium glucose cotransporter (SGLT2) inhibitors, exhibits antidiabetic efficacy in rodent models. J. Pharmacol. Exp. Ther. 2008, 327, 268-276.
29. Bickel, M.; Brummerhop, H.; Frick, W.; Glombik, H.; Herling, A.W.; Heuer, H.O.; Plettenburg, O.; Theis, S.; Werner, U.; Kramer, W. Effects of AVE2268, a substituted glycopyranoside, on urinary glucose excretion and blood glucose in mice and rats. Arzneimittelforschung 2008, 58, 574-580.
30. Derdau, V.; Fey, T.; Atzrodt, J. Synthesis of isotopically labelled SGLT inhibitors and their metabolites. Tetrahedron 2010, 66, 1472-1482.
31. Fujimori, Y.; Katsuno, K.; Ojima, K.; Nakashima, I.; Nakano, S.; Ishikawa-Takemura, Y.; Kusama, H.; Isaji, M. Sergliflozin etabonate, a selective SGLT2 inhibitor, improves glycemic control in streptozotocin-induced diabetic rats and Zucker fatty rats. Eur. J. Pharmacol. 2009, 609, 148-154.
32. Katsuno, K.; Fujimori, Y.; Ishikawa-Takemura, Y.; Isaji, M. Long-term treatment with sergliflozin etabonate improves disturbed glucose metabolism in KK-A(y) mice. Eur. J. Pharmacol. 2009, 618, 98-104.
33. Hussey, E.K.; Clark, R.V.; Amin, D.M.; Kipnes, M.S.; O'Connor-Semmes, R.L.; O'Driscoll, E.C.; Leong, J.; Murray, S.C.; Dobbins, R.L.; Layko, D.; et al. Single-dose pharmacokinetics and pharmacodynamics of sergliflozin etabonate, a novel inhibitor of glucose reabsorption, in healthy volunteers and patients with type 2 diabetes mellitus. J. Clin. Pharmacol. 2010, 50, 623-635.
34. Hussey, E.K.; Dobbins, R.L.; Stoltz, R.R.; Stockman, N.L.; O'Connor-Semmes, R.L.; Kapur, A.; Murray, S.C.; Layko, D.; Nunez, D.J. Multiple-dose pharmacokinetics and pharmacodynamics of sergliflozin etabonate, a novel inhibitor of glucose reabsorption, in healthy overweight and obese subjects: A randomized double-blind study. J. Clin. Pharmacol. 2010, 50, 636-646.
35. Dobbins, R.L.; O'Connor-Semmes, R.; Kapur, A.; Kapitza, C.; Golor, G.; Mikoshiba, I.; Tao, W.; Hussey, E.K. Remogliflozin etabonate, a selective inhibitor of the sodium-dependent transporter 2 reduces serum glucose in type 2 diabetes mellitus patients. Diabetes Obes. Metab. 2012, 14, 15-22.
36. Mudaliar, S.; Armstrong, D.A.; Mavian, A.A.; O'Connor-Semmes, R.; Mydlow, P.K.; Ye, J.; Hussey, E.K.; Nunez, D.J.; Henry, R.R.; Dobbins, R.L. Remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2, improves serum glucose profiles in type 1 diabetes. Diabetes Care 2012, 35, 2198-2200.
37. Hussey, E.K.; Kapur, A.; O'Connor-Semmes, R.; Tao, W.; Rafferty, B.; Polli, J.W.; James, C.D., Jr.; Dobbins, R.L. Safety, pharmacokinetics and pharmacodynamics of remogliflozin etabonate, a novel SGLT2 inhibitor, and metformin when co-administered in subjects with type 2 diabetes mellitus. BMC Pharmacol. Toxicol. 2013, 14, 25.
38. Kapur, A.; O'Connor-Semmes, R.; Hussey, E.K.; Dobbins, R.L.; Tao, W.; Hompesch, M.; Smith, G.A.; Polli, J.W.; James, C.D., Jr.; Mikoshiba, I.; et al. First human dose-escalation study with remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2 (SGLT2), in healthy subjects and in subjects with type 2 diabetes mellitus. BMC Pharmacol. Toxicol. 2013, 14, 26.
39. Sykes, A.P.; O'Connor-Semmes, R.; Dobbins, R.; Dorey, D.J.; Lorimer, J.D.; Walker, S.; Wilkison, W.O.; Kler, L. Randomized trial showing efficacy and safety of twice-daily remogliflozin etabonate for the treatment of type 2 diabetes. Diabetes Obes. Metab. 2015, 17, 94-97.
40. Sykes, A.P.; Kemp, G.L.; Dobbins, R.; O'Connor-Semmes, R.; Almond, S.R.; Wilkison, W.O.; Walker, S.; Kler, L. Randomized efficacy and safety trial of once-daily remogliflozin etabonate for the treatment of type 2 diabetes. Diabetes Obes. Metab. 2015, 17, 98-101.
41. O'Connor-Semmes, R.; Walker, S.; Kapur, A.; Hussey, E.K.; Ye, J.; Wang-Smith, L.; Tao, W.; Dobbins, R.L.; Cheatham, B.; Wilkison, W.O. Pharmacokinetics and pharmacodynamics of the SGLT2 inhibitor remogliflozin etabonate in subjects with mild and moderate renal impairment. Drug Metab. Dispos. 2015, 43, 1077-1083.
42. Link, J.T.; Sorensen, B.K. A method for preparing C-glycosides related to phlorizin. Tetrahedron Lett. 2000, 41, 9213-9217.
43. Meng, W.; Ellsworth, B.A.; Nirschl, A.A.; McCann, P.J.; Patel, M.; Girotra, R.N.; Wu, G.; Sher, P.M.; Morrison, E.P.; Biller, S.A.; et al. Discovery of dapagliflozin: A potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J. Med. Chem. 2008, 51, 1145-1149.
44. Han, S.; Hagan, D.L.; Taylor, J.R.; Xin, L.; Meng, W.; Biller, S.A.; Wetterau, J.R.; Washburn, W.N.; Whaley, J.M. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes 2008, 57, 1723-1729.
45. Komoroski, B.; Vachharajani, N.; Feng, Y.; Li, L.; Kornhauser, D.; Pfister, M. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin. Pharmacol. Ther. 2009, 85, 513-519.
46. List, J.F.; Woo, V.; Morales, E.; Tang, W.; Fiedorek, F.T. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 2009, 32, 650-657.
47. Wilding, J.P.; Norwood, P.; T'joen, C.; Bastien, A.; List, J.F.; Fiedorek, F.T. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: Applicability of a novel insulin-independent treatment. Diabetes Care 2009, 32, 1656-1662.
48. Ferrannini, E.; Ramos, S.J.; Salsali, A.; Tang, W.; List, J.F. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: A randomized, double-blind, placebo-controlled, phase III trial. Diabetes Care 2010, 33, 2217-2224.
49. Bailey, C.J.; Gross, J.L.; Pieters, A.; Bastien, A.; List, J.F. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: A randomised, double-blind, placebo-controlled trial. Lancet 2010, 375, 2223-2233.
50. Strojek, K.; Yoon, K.H.; Hruba, V.; Elze, M.; Langkilde, A.M.; Parikh, S. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: A randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes. Metab. 2011, 13, 928-938.
51. Nauck, M.A.; Del Prato, S.; Meier, J.J.; Durán-García, S.; Rohwedder, K.; Elze, M.; Parikh, S.J. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: A randomized, 52-week, double-blind, active controlled noninferiority trial. Diabetes Care 2011, 34, 2015-2022.
52. Rosenstock, J.; Vico, M.; Wei, L.; Salsali, A.; List, J.F. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA1c, body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care 2012, 35, 1473-1478.
53. Nomura, S.; Sasamaki, S.; Hongu, M.; Kawanishi, E.; Koga, Y.; Sakamoto, T.; Yamamoto, Y.; Ueta, K.; Kimata, H.; Nakayama, K.; et al. Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus. J. Med. Chem. 2010, 53, 6355-6360.
54. Rosenstock, J.; Aggarwal, N.; Polidori, D.; Zhao, Y.; Arbit, D.; Usiskin, K.; Capuano, G.; Canovatchel, W.; Canagliflozin DIA 2001 Study Group. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes. Diabetes Care 2012, 35, 1232-1238.
55. Devineni, D.; Morrow, L.; Hompesch, M.; Skee, D.; Vandebosch, A.; Murphy, J.; Ways, K.; Schwartz, S. Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin. Diabetes Obes. Metab. 2012, 14, 539-545.
56. Stenlöf, K.; Cefalu, W.T.; Kim, K.A.; Alba, M.; Usiskin, K.; Tong, C.; Canovatchel, W.; Meininger, G. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes. Metab. 2013, 15, 372-382.
57. Yale, J.F.; Bakris, G.; Cariou, B.; Yue, D.; David-Neto, E.; Xi, L.; Figueroa, K.; Wajs, E.; Usiskin, K.; Meininger, G. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes. Metab. 2013, 15, 463-473.
58. Grampler, R.; Thomas, L.; Eckhardt, M.; Himmelsbach, F.; Sauer, A.; Sharp, D.E.; Bakker, R.A.; Mark, M.; Klein, T.; Eickelmann, P. Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: Characterisation and comparison with other SGLT-2 inhibitors. Diabetes Obes. Metab. 2012, 14, 83-90.
59. Mudaliar, S.; Polidori, D.; Zambrowicz, B.; Henry, R.R. Sodium-glucose cotransporter inhibitors: Effects on renal and intestinal glucose transport: From bench to bedside. Diabetes Care 2015, 38, 2344-2353.
60. Sato, S.; Takeo, J.; Aoyama, C.; Kawahara, H. Na+ -glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens. Bioorg. Med. Chem. 2007, 15, 3445-3449.
61. Yang, J.; Yang, X.; Wang, C.; Lin, Q.; Mei, Z.; Zhao, P. Sodium-glucose-linked transporter 2 inhibitors from Sophora flavescens. Med. Chem. Res. 2015, 24, 1265-1271.
62. + -glucose cotransporter (SGLT) inhibitors from Acer nikoense. Bioorg. Med. Chem. Letter. 2010, 20, 1070-1074.
63. Arai, H.; Hirasawa, Y.; Rahman, A.; Kusumawati, I.; Zaini, N.C.; Sato, S.; Aoyama, C.; Takeo, J.; Morita, H. Alstiphyllanines E-H, picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter. Bioorg. Med. Chem. 2010, 18, 2152-2158.
64. Shimokawa, Y.; Akao, Y.; Hirasawa, Y.; Awang, K.; Hadi, A.H.; Sato, S.; Aoyama, C.; Takeo, J.; Shiro, M.; Morita, H. Gneyulins A and B, stilbene trimers, and noidesols A and B, dihydroflavonol-C-glucosides, from the bark of Gnetum gnemonoides. J. Nat. Prod. 2010, 73, 763-767.
65. He, X.; Fang, J.; Huang, L.; Wang, J.; Huang, X. Sophora flavescens Ait.: Traditional usage, phytochemistry and pharmacology of an important traditional Chinese medicine. J. Ethnopharmacol. 2015, 172, 10-29.
66. Nagai, M.; Kubo, M.; Fujita, M.; Inoue, T.; Matsuo, M. Studies on the constituents of Aceraceae plants. II. Structure of aceroside I, a glucose of a novel cyclic diarylheptanoids from Acer nikoense Maxim. Chem. Pharm. Bull. (Tokyo) 1978, 26, 2805-2810.
67. Changwichit, K.; Khorana, N.; Suwanborirux, K.; Waranuch, N.; Limpeanchob, N.; Wisuitiprot, W.; Suphrom, N.; Ingkaninan, K. Bisindole alkaloids and secoiridoids from Alstonia macrophylla Wall. ex G. Don. Fitoterapia 2011, 82, 798-804.
68. Khyade, M.S.; Kasote, D.M.; Vaikos, N.P. Alstonia scholaris (L.) R. Br. and Alstonia macrophylla Wall. ex G. Don: A comparative review on traditional uses, phytochemistry and pharmacology. J. Ethnopharmacol. 2014, 153, 1-18.
69. Huang, T.; Shen, P.; Shen, Y. Preparative separation and purification of deoxyschisandrin and gamma-schisandrin from Schisandra chinensis (Turcz.) Baill by high-seed counter-current chromatography. J. Chromatogr. A 2005, 1066, 239-242.
70. Chan, S.W. Panax ginseng, Rhodiola rosea and Schisandra chinensis. Int. J. Food Sci. Nutr. 2012, 63, 75-81.
71. Qu, Y.; Chan, J.Y.; Wong, C.W.; Cheng, L.; Xu, C.; Leung, A.W.; Lau, C.B. Antidiabetic effect of Schisandrae Chinensis Fructus involves inhibition of the sodium glucose cotransporter. Drug Dev. Res. 2015, 76, 1-8.
72. INVOKANA® (Canagliflozin) Prescribing Information. Available online: http://www.accessdata.fda.gov/drugsatfda-docs/label/2016/204042s015s019lbl.pdf (accessed on 12 August 2016).
73. JARDIANCE® (Empagliflozin) Prescribing Information. Available online: http://www.accessdata.fda.gov/drugsatfda-docs/label/2016/204629s005lbl.pdf (accessed on 12 August 2016).
74. Wu, J.S.; Peng, Y.H.; Wu, J.M.; Hsieh, C.J.; Wu, S.H.; Coumar, M.S.; Song, J.S.; Lee, J.C.; Tsai, C.H.; Chen, C.T.; et al. Discovery of non-glycoside sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors by ligand-based virtual screening. J. Med. Chem. 2010, 53, 8770-8774.
75. Devineni, D.; Vaccaro, N.; Murphy, J.; Curtin, C.; Mamidi, R.N.; Weiner, S.; Wang, S.S.; Ariyawansa, J.; Stieltjes, H.; Wajs, E.P.; et al. Effects of rifampin, cyclosporine A, and probenecid on the pharmacokinetic profile of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in healthy participants. Int. J. Clin. Pharmacol. Ther. 2015, 53, 115-128.