Targeting aldose reductase for the treatment of diabetes complications and inflammatory diseases: New insights and future directions

Journal of Medicinal Chemistry

Volumn 58, Issue 5, 2015, Pages 2047-2067

  Maccari, Rosanna ^a   Ottanà, Rosaria ^a  

^a UNIVERSITY OF MESSINA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE REDUCTASE; ALDOSE REDUCTASE INHIBITOR; ANTIOXIDANT; CARBONYL REDUCTASE; ENZYME INHIBITOR;

ANTIOXIDANT ACTIVITY; ARTICLE; DIABETES MELLITUS; DRUG BIOAVAILABILITY; DRUG DESIGN; ENZYME STRUCTURE; HUMAN; INFLAMMATORY DISEASE; NONHUMAN; OXIDATIVE STRESS; TREATMENT OUTCOME; ANTAGONISTS AND INHIBITORS; DIABETES COMPLICATIONS; INFLAMMATION;

ALDEHYDE REDUCTASE; DIABETES COMPLICATIONS; DIABETES MELLITUS; ENZYME INHIBITORS; HUMANS; INFLAMMATION;

EID: 84924709733     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500907a     Document Type: Article

References (167)

1. Brownlee, M. Biochemistry and Molecular Cell Biology of Diabetic Complications Nature 2001, 414, 813-820
2. Brownlee, M. The Pathobiology of Diabetic Complications. A Unifying Mechanism Diabetes 2005, 54, 1615-1625
3. Yabe-Nishimura, C. Aldose Reductase in Glucose Toxicity: A Potential Target for the Prevention of Diabetic Complications Pharmacol. Rev. 1998, 50, 21-33
4. Costantino, L.; Rastelli, G.; Cignarella, G.; Vianello, P.; Barlocco, D. New Aldose Reductase Inhibitors as Potential Agents for the Prevention of Long-Term Diabetic Complications Exp. Opin. Ther. Pat. 1997, 7, 843-858
5. Costantino, L.; Rastelli, G.; Vianello, P.; Cignarella, G.; Barlocco, D. Diabetes Complications and Their Potential Prevention: Aldose Reductase Inhibition and Other Approaches Med. Res. Rev. 1999, 19, 3-23
6. Costantino, L.; Rastelli, G.; Gamberini, M. C.; Barlocco, D. Pharmacological Approaches to the Treatment of Diabetic Complications Exp. Opin. Ther. Pat. 2000, 10, 1245-1262
7. Del Corso, A.; Cappiello, M.; Mura, U.; From, A. Dull Enzyme to Something Else: Facts and Perspectives Regarding Aldose Reductase Curr. Med. Chem. 2008, 15, 1452-1461
8. Srivastava, S. K.; Ramana, K. V.; Bhatnagar, A. Role of Aldose Reductase and Oxidative Damage in Diabetes and the Consequent Potential for Therapeutic Options Endocr. Rev. 2005, 26, 380-392
9. Banditelli, S.; Boldrini, E.; Vilardo, P. G.; Cecconi, I.; Cappiello, M.; Dal Monte, M.; Marini, I.; Del Corso, A.; Mura, U. A New Approach against Sugar Cataract through Aldose Reductase Inhibitors Exp. Eye Res. 1999, 69, 533-538
10. Hotta, N.; Toyota, T.; Matsuoka, K.; Shigeta, Y.; Kikkawa, R.; Kaneko, T.; Takahashi, A.; Sugimura, K.; Koike, Y.; Ishii, J.; Sakamoto, N. Clinical Efficacy of Fidarestat, a Novel Aldose Reductase Inhibitor, for Diabetic Peripheral Neuropathy Diabetes Care 2001, 24, 1776-1782
11. Asano, T.; Saito, Y.; Kawakami, M.; Yamada, N. Fidarestat (SNK-860), a Potent Aldose Reductase Inhibitor, Normalizes the Elevated Sorbitol Accumulation in Erythrocytes of Diabetic Patients J. Diabetes Complications 2002, 16, 133-138
12. Okayama, N.; Omi, H.; Okouchi, M.; Imaeda, K.; Kato, T.; Akao, M.; Imai, S.; Shimizu, M.; Fukutomi, T.; Itoh, M. Mechanisms of Inhibitory Activity of the Aldose Reductase Inhibitor, Epalrestat, on High Glucose-Mediated Endothelial Injury: Neutrophil-Endothelial Cell Adhesion and Surface Expression of Endothelial Adhesion Molecules J. Diabetes Complications 2002, 16, 321-326
13. Nakahara, M.; Miyata, K.; Otani, S.; Miyai, T.; Nejima, R.; Yamagami, S.; Amano, S. A Randomised, Placebo Controlled Clinical Trial of the Aldose Reductse Inhibitor CT-112 as Management of Corneal Epithelial Disorders in Diabetic Patients Br. J. Ophthalmol. 2005, 89, 266-268
14. Hotta, N.; Akanuma, Y.; Kawamori, R.; Matsuoka, K.; Oka, Y.; Shichiri, M.; Toyota, T.; Nakashima, M.; Yoshimura, I.; Sakamoto, N.; Shigeta, Y. Long-Term Clinical Effects of Epalrestat, an Aldose Reductase Inhibitor, on Diabetic Peripheral Neuropathy Diabetes Care 2006, 29, 1538-1544
15. Oyama, T.; Miyasita, Y.; Watanabe, H.; Shirai, K. The Role of Polyol Pathway in High Glucose-Induced Endothelial Cell Damages Diabetes Res. Clin. Pract. 2006, 73, 227-234
16. Lorenzi, M. The Polyol Pathway as a Mechanism for Diabetic Retinopathy: Attractive, Elusive, and Resilient Exp. Diabetes Res. 2007, 61038 10.1155/2007/61038
17. Matsumoto, T.; Ono, Y.; Kurono, M.; Kuromiya, A.; Nakamura, K.; Bril, V. Ranirestat (AS-3201), a Potent Aldose Reductase Inhibitor, Reduces Sorbinil Levels and Improves Motor Nerve Conduction Velocity in Streptozotocin-Diabetes Rats J. Pharmacol. Sci. 2008, 107, 231-237
18. Schemmel, K. E.; Padiyara, R. S.; D'Souza, J. J. Aldose Reductase Inhibitors in the Treatment of Diabetic Peripheral Neuropathy: A Review J. Diabetes Complications 2010, 24, 354-360
19. Miyamoto, S. Molecular Modeling and Structure-Based Drug Discovery Studies of Aldose Reductase Inhibitors Chem-Bio Inf. J. 2002, 2, 74-85
20. Suzen, S.; Buyukbingol, E. Recent Studies of Aldose Reductase Enzyme Inhibition for Diabetic Complications Curr. Med. Chem. 2003, 10, 1329-1352
21. Alexiou, P.; Pegklidou, K.; Chatzopoulou, M.; Nicolaou, I.; Demopoulos, V. J. Aldose Reductase Enzyme and Its Implication to Major Health Problems of the 21st Century Curr. Med. Chem. 2009, 16, 734-752
22. Maccari, R.; Ottanà, R. 2,4-Thiazolidinedione and 2-Thioxo-4-thiazolidinone Derivatives as Aldose Reductase Inhibitors in the Search for Drugs To Prevent Long-Term Diabetes Complications. In Advances in Molecular Mechanisms and Pharmacology of Diabetic Complications; Stefek, M. Ed.; Transworld Research Network: Kerala, India, 2010; pp 219-245.
23. Hotta, N.; Kawamori, R.; Atsumi, Y.; Baba, M.; Kishikawa, H.; Nakamura, J.; Oikawa, S.; Yamada, N.; Yasuda, H.; Shigeta, Y. Stratified Analyses for Selecting Appropriate Target Patients with Diabetic Peripheral Neuropathy for Long-Term Treatment with an Aldose Reductase Inhibitor, Epalrestat Diabetic Med. 2008, 25, 818-825
24. Ramirez, M. A.; Borja, N. L. Epalrestat: An Aldose Reductase Inhibitor for the Treatment of Diabetic Neuropathy Pharmacotherapy 2008, 28, 646-655
25. Sarges, R.; Schnur, R. C.; Belletire, J. L.; Peterson, M. J. Spiro Hydantoin Aldose Reductase Inhibitor J. Med. Chem. 1988, 31, 230-243
26. Lipinski, C. A.; Aldinger, C. E.; Beyer, T. A.; Bordner, J.; Burdi, D. F.; Bussolotti, D. L.; Inskeep, P. B.; Siegel, T. W. Hydantoin Bioisosteres. In Vivo Active Spiro Hydroxy Acetic Acid Aldose Reductase Inhibitors J. Med. Chem. 1992, 35, 2169-2177
27. Sestanj, K.; Bellini, F.; Fung, S.; Abraham, N.; Treasurywala, A.; Humber, L.; Simard-Duquesne, N.; Dvornik, D. N-[[5-(Trifluoromethyl)-6-methoxy-1-naphthalenyl]thioxomethyl]-N-methylglycine (Tolrestat), a Potent, Orally Active Aldose Reductase Inhibitor J. Med. Chem. 1984, 27, 255-256
28. Mylari, B. L.; Larson, E. R.; Beyer, T. A.; Zembrowski, W. J.; Aldinger, C. E.; Dee, M. F.; Siegel, T. W.; Singleton, D. H. Novel, Potent Aldose Reductase Inhibitors: 3,4-Dihydro-4-oxo-3-[[5-(trifluoromethyl)-2-benzothiazolyl]methyl]-1-phthalazine-acetic Acid (Zopolrestat) and Congeners J. Med. Chem. 1991, 34, 108-122
29. Hotta, N.; Yasuda, K.; Sumita, Y.; Sano, T.; Kakuta, H.; Nagashima, M.; Hayashi, Y.; Yamamoto, M.; Wakao, T.; Okuyama, M.; Kobayashi, M.; Mori, K. Effects of a Novel Aldose Reductase Inhibitor, Fidarestat (SNK-860), on Vibration Perception Threshold and Subjective Symptoms in Patients with Diabetic Polyneuropathy Clin. Drug Invest. 2004, 24, 671-680
30. Malamas, M. S.; Hohman, T. C.; Millen, J. Novel Spirosuccinimide Aldose Reductase Inhibitors Derived from Isoquinoline-1,3-diones: 2-[(4-Bromo-2-fluorophenyl)methyl]-6-fluorospiro[isoquinoline-4(1 H),3'-pyrrolidine]-1,2',3,5' (2 H)-tetrone and Congeners. I J. Med. Chem. 1994, 37, 2043-2058
31. Bril, V.; Hirose, T.; Tamioka, S.; Buchanan, R. Ranirestat for the Management of Diabetic Sensorimotor Polyneuropathy Diabetes Care 2009, 32, 1256-1260
32. Ward, W. H. J.; Sennitt, C. A.; Ross, H.; Dingle, A.; Timms, D.; Mirrlees, D. J.; Tuffin, D. P. Ponalrestat: A Potent and Specific Inhibitor of Aldose Reductase Biochem. Pharmacol. 1990, 39, 337-346
33. Ramana, K. V.; Friedrich, B.; Srivastava, S.; Bhatnagar, A.; Srivastava, S. K. Activation of Nuclear Factor-κB by Hyperglycemia in Vascular Smooth Muscle Cells Is Regulated by Aldose Reductase Diabetes 2004, 53, 2910-2920
34. Ramana, K. V.; Bhatnagar, A.; Srivastava, S. K. Inhibition of Aldose Reductase Attenuates TNF-α-Induced Expression of Adhesion Molecules in Endothelial Cells FASEB J. 2004, 18, 1209-1218
35. Ramana, K. V.; Srivastava, S. K. Mediation of Aldose Reductase in Lipopolysaccharide-Induced Inflammatory Signals in Mouse Peritoneal Macrophages Cytokine 2006, 36, 115-122
36. Yadav, U. C. S.; Srivastava, S. K.; Ramana, K. V. Aldose Reductase Inhibition Prevents Endotoxin-Induced Uveitis in Rats Invest. Ophthalmol. Visual Sci. 2007, 48, 4634-4642
37. Yadav, U. C. S.; Ramana, K. V.; Aguilera-Aguirre, L.; Boldogh, I.; Boulares, H. A.; Srivastava, S. K. Inhibition of Aldose Reductase Prevents Experimental Allergic Airway Inflammation in Mice PLoS One 2009, 4, e6535 10.1371/journal.pone.0006535
38. Reddy, A. B. M.; Ramana, K. V. Aldose Reductase Inhibition: Emerging Drug Target for the Treatment of Cardiovascular Complications Recent Pat. Cardiovasc. Drug Discovery 2010, 5, 25-32
39. Ramana, K. V. Aldose Reductase: New Insights for an Old Enzyme Biomol. Concepts 2011, 2, 103-114
40. Tang, W. H.; Martin, K. A.; Hwa, J. Aldose Reductase, Oxidative Stress, and Diabetic Mellitus Front. Pharmacol. 2012, 3, 87 10.3389/fphar.2012.00087
41. Pandey, S.; Srivastava, S. K.; Ramana, K. V. A Potential Therapeutic Role for Aldose Reductase Inhibitors in the Treatment of Endotoxin-Related Inflammatory Diseases Expert Opin. Invest. Drugs 2012, 21, 329-339
42. Jain, S.; Saraf, S. Type 2 Diabetes Mellitus-Its Global Prevalence and Therapeutic Strategies Diabetes Metab. Syndr.: Clin. Res. Rev. 2010, 4, 48-56
43. Gleissner, C. A.; Galkina, E.; Nadler, J. L.; Ley, K. Mechanisms by Which Diabetes Increases Cardiovascular Disease Drug Discovery Today: Dis. Mech. 2007, 4, 131-140
44. Turner, R. C.; Holman, R. R.; Cull, C. A.; Stratton, I. M.; Matthews, D. R.; Frighi, V.; Manley, S. E.; Neil, A.; McElroy, H.; Wright, D.; Kohner, E.; Fox, C.; Hadden, D. Intensive Blood-Glucose Control with Sulphonylureas or Insulin Compared with Conventional Treatment and Risk of Complications in Patients with Type 2 Diabetes (UKPDS 33) Lancet 1998, 352, 837-853
45. Srivastava, S.; Dixit, B. L.; Cai, J.; Sharma, S.; Hurst, H. E.; Bhatnagar, A.; Srivastava, S. K. Metabolism of Lipid Peroxidation Product, 4-Hydroxynonenal (HNE) in Rat Erythrocytes: Role of Aldose Reductase Free Radical Biol. Med. 2000, 29, 642-651
46. Vander Jagt, D. L.; Kolb, N. S.; Vander Jagt, T. J.; Chino, J.; Martinez, F. J.; Hunsaker, L. A.; Royer, R. E. Substrate Specificity of Human Aldose Reductase: Identification of 4-Hydroxynonenal as an Endogenous Substrate Biochim. Biophys. Acta 1995, 1249, 117-126
47. Evans, J. L.; Goldfine, I. D.; Maddux, B. A.; Grodsky, G. M. Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes Endocr. Rev. 2002, 23, 599-622
48. Williamson, J. R.; Chang, K.; Frangos, M.; Hasan, K. S.; Ido, Y.; Kawamura, T.; Nyengaard, J. R.; Van den Enden, M.; Kilo, C.; Tilton, R. G. Hyperglycemic Pseudohypoxia and Diabetic Complications Diabetes 1993, 42, 801-813
49. Hamada, Y.; Nakamura, J.; Naruse, K.; Komori, T.; Kato, K.; Kasuya, Y.; Nagai, R.; Horiuchi, S.; Hotta, N. Epalrestat, an Aldose Reductase Inhibitor, Reduces the Levels of N-(Carboxymethyl)lysine Protein Adducts and Their Precursors in Erythrocytes from Diabetic Patients Diabetes Care 2000, 23, 1539-1544
50. Roscic, M.; Horvat, S. Transformations of Bioactive Peptides in the Presence of Sugars-Characterization and Stability Studies of the Adducts Generated via the Maillard Reaction Bioorg. Med. Chem. 2006, 14, 4933-4943
51. Ramana, K. V.; Friedrich, B.; Tammali, R.; West, M. B.; Bhatnagar, A.; Srivastava, S. K. Requirement of Aldose Reductse for the Hyperglycemic Activation of Protein Kinase C and Formation of Diacylglycerol in Vascular Smooth Muscle Cells Diabetes 2005, 54, 818-829
52. Gleissner, C. A.; Sanders, J.M.; Nadler, J.; Ley, K. Upregulation of Aldose Reductase During Foam Cell Formation as Possible Link Among Diabetes, Hyperlipidemia, and Atherosclerosis Arterioscler., Thromb., Vasc. Biol. 2008, 28, 1137-1143
53. Srivastava, S. K.; Yadav, U. C. S.; Reddy, A. B. M.; Saxena, A.; Tammali, R.; Shoeb, M.; Ansari, N. H.; Bhatnagar, A.; Petrash, M. J.; Srivastava, S.; Ramana, K. V. Aldose Reductase Inhibition Suppresses Oxidative Stress-Induced Inflammatory Disorders Chem.-Biol. Interact. 2011, 191, 330-338
54. Shoeb, M.; Ansari, N. H.; Srivastava, S. K.; Ramana, K. V. 4-Hydroxynonenal in the Pathogenesis and Progression of Human Diseases Curr. Med. Chem. 2014, 21, 230-237
55. Gupta, S. C.; Sundaram, C.; Reuter, S.; Aggarwal, B. B. Inhibiting NF-κB Activation by Small Molecules as a Therapeutic Strategy Biochim. Biophys. Acta 2010, 1799, 775-787
56. Luis-Rodriguez, D.; Martinez-Castelao, A.; Gorriz, J. L.; de Alvaro, F.; Navarro-Gonzalez, J. F. Pathophysiological Role and Therapeutic Implications of Inflammation in Diabetic Nephropathy World J. Diabetes 2012, 3, 7-18
57. Plutzky, J. Inflammation in Atherosclerosis and Diabetes Mellitus Rev. Endocr. Metab. Dis. 2004, 5, 255-259
58. Schmidt, M. I.; Saad, M. J. A.; Duncan, B. B. Subclinical Inflammation and Obesity, Diabetes and Related Disorders Drug Discovery Today: Dis. Mech. 2005, 2, 307-312
59. Frohnert, B. I.; Long, E. K.; Hahn, W. S.; Bernlohr, D. A. Glutathionylated Lipid Aldehydes Are Products of Adipocyte Oxidative Stress and Activators of Macrophage Inflammation Diabetes 2014, 63, 89-100
60. Vedantham, S.; Thiagarajan, D.; Ananthakrishnan, R.; Wang, L.; Rosario, R.; Zou, Y. S.; Goldberg, I.; Yan, S. F.; Schmidt, A. M.; Ramasamy, R. Aldose Reductase Drives Hyperacetylation of Erg-1 in Hyperglycemia and Consequent Upregulation of Proinflammatory and Prothrombotic Signals Diabetes 2014, 63, 761-774
61. Zozulinska, D.; Wierusz-Wysocka, B. Type 2 Diabetes Mellitus as Inflammatory Disease Diabetes Res. Clin. Pract. 2006, 74S, S12-S16
62. Oates, P. J.; Mylari, B. L. Aldose Reductase Inhibitors: Therapeutic Implications for Diabetic Complications Expert. Opin. Invest. Drugs 1999, 8, 2095-2119
63. Heesom, A. E.; Hibberd, M. L.; Millward, A.; Demaine, A. G. Polymorphism in the 5'-End of the Aldose Reductase Gene Is Strongly Associated with the Development of Diabetic Nephopathy in Type 1 Diabetes Diabetes 1997, 46, 287-291
64. Kao, Y. L.; Donaghue, K.; Chan, A.; Knight, J.; Silink, M. A Novel Polymorphism in the Aldose Reductase Gene Promoter Region Is Strongly Associated with Diabetic Retinopathy in Adolescents with Type 1 Diabetes Diabetes 1999, 48, 1338-1340
65. Lajer, M.; Tarnow, L.; Fleckner, J.; Hansen, B. V.; Edwards, D. G.; Parving, H. H.; Boel, E. Association of Aldose Reductase Gene Z+2 Polymorphism with Reduced Susceptibility to Diabetic Nephropathy in Caucasian Type 1 Diabetic Patients Diabetic Med. 2004, 21, 867-873
66. Sivenius, K.; Niskanen, L.; Voutilainen-Kaunisto, R.; Laakso, M.; Uusitupa, M. Aldose Reductase Gene Polymorphisms and Susceptibility to Microvascular Complications in Type 2 Diabetes Diabetic Med. 2004, 21, 1325-1333
67. Sivenius, K.; Pihlajamaki, J.; Partanen, J.; Niskanen, L.; Laakso, M.; Uusitupa, M. Aldose Reductase Gene Polymorphisms and Peripheral Nerve Function in Patients with Type 2 Diabetes Diabetes Care 2004, 27, 2021-2026
68. Tammali, R.; Srivastava, S. K.; Ramana, K. V. Targeting Aldose Reductase for the Treatment of Cancer Curr. Cancer Drug Targets 2011, 11, 560-571
69. Ramana, K. V.; Srivastava, S. K. Aldose Reductase: A Novel Therapeutic Target for Inflammatory Pathologies Int. J. Biochem. Cell Biol. 2010, 42, 17-20
70. Reuter, S.; Gupta, S. C.; Chaturvedi, M. M.; Aggarwal, B. B. Oxidative Stress, Inflammation, and Cancer: How Are They Linked? Free Radical Biol. Med. 2010, 49, 1603-1616
71. Panico, A.; Maccari, R.; Cardile, V.; Crascì, L.; Ronsisvalle, S.; Ottanà, R. 5-Arylidene-4-thiazolidinone Derivatives Active as Antidegenerative Agents on Human Chondrocyte Cultures Med. Chem. 2013, 9, 84-90
72. Maccari, R.; Vitale, R. M.; Ottanà, R.; Rocchiccioli, M.; Marrazzo, A.; Cardile, V.; Graziano, A. C. E.; Amodeo, P.; Mura, U.; Del Corso, A. Structure-Activity Relationships and Molecular Modelling of New 5-Arylidene-4-thiazolidinone Derivatives as Aldose Reductase Inhibitors and Potential Anti-Inflammatory Agents Eur. J. Med. Chem. 2014, 81, 1-14
73. Chang, K.-C.; Laffin, B.; Ponder, J.; énzsöly, A.; Németh, J.; LaBarbera, D. V.; Petrash, J. M. Beta-Glucogallin Reduces the Expression of Lipopolysaccharide-Induced Inflammatory Markers by Inhibition of Aldose Reductase in Murine Macrophages and Ocular Tissues Chem.-Biol. Interact. 2013, 202, 283-287
74. Zeng, K.-W.; Li, J.; Dong, X.; Wang, Y.-H.; Ma, Z.-Z.; Jiang, Y.; Jin, H.-W.; Tu, P.-F. Anti-Neuroinflammatory Efficacy of the Aldose Reductase Inhibitor FMHM via Phospholipase C/Protein Kinase C-Dependent NF-κB and MAPK Pathways Toxicol. Appl. Pharmacol. 2013, 273, 159-171
75. Hwang, Y. C.; Kaneko, M.; Bakr, S.; Liao, H.; Lu, Y.; Lewis, E. R.; Yan, S.; Ii, S.; Itakura, M.; Rui, L.; Skopicki, H.; Homma, S.; Schmidt, A. M.; Oates, P. J.; Szabolcs, M.; Ramasamy, R. Central Role for Aldose Reductase Pathway in Myocardial Ischemic Injury FASEB J. 2004, 18, 1192-1199
76. Son, N.-H.; Ananthakrishnan, R.; Yu, S.; Khan, R. S.; Jiang, H.; Ji, R.; Akashi, H.; Li, Q.; O'Shea, K.; Homma, S.; Goldberg, I. J.; Ramasamy, R. Cardiomyocyte Aldose Reductase Causes Heart Failure and Impairs Recovery from Ischemia PLoS One 2012, 7, e46549 10.1371/journal.pone.0046549
77. Laffin, B.; Petrash, J. M. Expression of the Aldo-Ketoreductases AKR1B1 and AKR1B10 in Human Cancers Front. Pharmacol. 2012, 3, 104 10.3389/fphar.2012.00104
78. Plebuch, M.; Soldan, M.; Hungerer, C.; Koch, L.; Maser, E. Increased Resistance of Tumor Cells to Daunorubicin after Transfection of cDNAs Coding for Anthracycline Inactivating Enzymes Cancer Lett. 2007, 255, 49-56
79. Der-Torossian, H.; Wysong, A.; Shadfar, S.; Willis, M. S.; McDunn, J.; Couch, M. E. Metabolic Derangements in the Gastrocnemius and the Effect of Compound A Therapy in a Murine Model of Cancer Cachexia J. Cachexia Sarcopenia Muscle 2013, 4, 145-155
80. Kawamura, I.; Lacey, E.; Yamamoto, N.; Sakai, F.; Takeshita, S.; Inami, M.; Nishigaki, F.; Naoe, Y.; Tsujimoto, S.; Manda, T.; Shimomura, K.; Goto, T. Ponalrestat, an Aldose Reductase Inhibitor, Inhibits Cachexia Syndrome Induced by Colon26 Adenocarcinoma in Mice Anticancer Res. 1999, 19, 4105-4111
81. Tammali, R.; Ramana, K. V.; Singhal, S. S.; Awasthi, S.; Srivastava, S. K. Aldose Reductase Regulates Growth Factor-Induced Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Human Colon Cancer Cells Cancer Res. 2006, 66, 9705-9713
82. Tammali, R.; Ramana, K. V.; Srivastava, S. K. Aldose Reductase Regulates TNF-α-Induced PGE2 Production in Human Colon Cancer Cells Cancer Lett. 2007, 252, 299-306
83. Shoeb, M.; Ramana, K. V.; Srivastava, S. K. Aldose Reductase Inhibition Enhances TRAIL-Induced Human Colon Cancer Cell Apoptosis through AKT/FOXO3a-dependent Upregulation of Death Receptors Free Radical Biol. Med. 2013, 63, 280-290
84. Tammali, R.; Reddy, A. B. M.; Srivastava, S. K.; Ramana, K. V. Inhibition of Aldose Reductase Prevents Angiogenesis in Vitro and in Vivo Angiogenesis 2011, 14, 209-221
85. Wilson, D. K.; Bohren, K. M.; Gabbay, K. H.; Quiocho, F. A. An Unlikely Sugar Substrate Site in the 1.65 Structure of the Human Aldose Reductase Holoenzyme Implicated in Diabetic Complications Science 1992, 257, 81-84
86. Rondeau, J. M.; Tête-Favier, F.; Podjarny, A.; Reymann, J. M.; Barth, P.; Biellmann, J. F.; Moras, D. Novel NADPH-Binding Domain Revealed by the Crystal Structure of Aldose Reductase Nature 1992, 355, 469-472
87. Urzhumtsev, A.; Tête-Favier, F.; Mitschler, A.; Barbanton, J.; Barth, P.; Urzhumtseva, L.; Biellmann, J.-F.; Podjarny, A. D.; Moras, D. A 'Specificity' Pocket Inferred from the Crystal Structures of the Complexes of Aldose Reductase with the Pharmaceutically Important Inhibitors Tolrestat and Sorbinil Structure 1997, 5, 601-612
88. El-Kabbani, O.; Darmanin, C.; Schneider, T. R.; Hazemann, I.; Ruiz, F.; Oka, M.; Joachimiak, A.; Schulze-Briese, C.; Tomizaki, T.; Mitschler, A.; Podjarny, A. Ultrahigh Resolution Drug Design. II. Atomic Resolution Structures of Human Aldose Reductase Holoenzyme Complexed with Fidarestat and Minalrestat: Implications for the Binding of Cyclic Imide Inhibitors Proteins 2004, 55, 805-813
89. Wilson, D. K.; Tarle, I.; Petrash, J. M.; Quiocho, F. A. Refined 1.8 Å Structure of Human Aldose Reductase Complexed with the Potent Inhibitor Zopolrestat Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 9847-9851
90. Biadene, M.; Hazemann, I.; Cousido, A.; Ginell, S.; Joachimiak, A.; Sheldrick, G. M.; Podjarny, A.; Schneider, T. R. The Atomic Resolution Structure of Human Aldose Reductase Reveals That Rearrangement of a Bound Ligand Allows the Opening of the Safety-Belt Loop Acta Crystallogr. 2007, D63, 665-672
91. Bohren, K. M.; Brownlee, J. M.; Milne, A. C.; Gabbay, K. H.; Harrison, D. H.T. The Structure of Apo R268A Human Aldose Reductase: Hinges and Latches That Control the Kinetic Mechanism Biochim. Biophys. Acta 2005, 1748, 201-212
92. Sotriffer, C. A.; Krämer, O.; Klebe, G. Probing Flexibility and 'Induced-Fit' Phenomena in Aldose Reductase by Comparative Crystal Structure Analysis and Molecular Dynamics Simulations Proteins 2004, 56, 52-66
93. Krämer, O.; Hazemann, I.; Podjarny, A. D.; Klebe, G. Virtual Screening for Inhibitors of Human Aldose Reductase Proteins 2004, 55, 814-23
94. Steuber, H.; Heine, A.; Podjarny, A.; Klebe, G. Merging the Binding Sites of Aldose and Aldehyde Reductase for Detection of Inhibitor Selectivity-Determining Features J. Mol. Biol. 2008, 379, 991-1016
95. Steuber, H.; Zentgraf, M.; Gerlach, C.; Sotriffer, C. A.; Heine, A.; Klebe, G. Expect the Unexpected or Caveat for Drug Designers: Multiple Structure Determinations Using Aldose Reductase Crystals Treated under Varying Soaking and Co-Crystallisation Conditions J. Mol. Biol. 2006, 363, 174-187
96. Dixit, B. L.; Balendiran, G. K.; Watowich, S. J.; Srivastava, S.; Ramana, K. V.; Petrash, J. M.; Bhatnagar, A.; Srivastava, S. K. Kinetic and Structural Characterization of the Glutathione-Binding Site of Aldose Reductase J. Biol. Chem. 2000, 275, 21587-21595
97. Singh, R.; White, M. A.; Ramana, K. V.; Petrash, J. M.; Watowich, S. J.; Bhatnagar, A.; Srivastava, S. K. Structure of a Glutathione Conjugate Bound to the Active Site of Aldose Reductase Proteins 2006, 64, 101-110
98. Ramana, K. V.; Dixit, B. L.; Srivastava, S.; Balendiran, G. K.; Srivastava, S. K.; Bhatnagar, A. Selective Recognition of Glutathiolated Aldehydes by Aldose Reductase Biochemistry 2000, 39, 12172-12180
99. Petrash, J. M.; Harter, T. M.; Devine, C. S.; Olins, P. O.; Bhatnagar, A.; Liu, S.; Srivastava, S. K. Involvement of Cysteine Residues in Catalysis and Inhibition of Human Aldose Reductase J. Biol. Chem. 1992, 267, 24833-24840
100. Cappiello, M.; Vilardo, P. G.; Micheli, V.; Jacomelli, G.; Banditelli, S.; Leverenz, V.; Giblin, F. J.; Del Corso, A.; Mura, U. Thiol Disulfide Exchange Modulates the Activity of Aldose Reductase in Intact Bovine Lens as a Response to Oxidative Stress Exp. Eye Res. 2000, 70, 795-803
101. Cappiello, M.; Voltarelli, M.; Giannessi, M.; Cecconi, I.; Camici, G.; Manao, G.; Del Corso, A.; Mura, U. Glutathione Dependent Modification of Bovine Lens Aldose Reductase Exp. Eye Res. 1994, 58, 491-501
102. Cappiello, M.; Vilardo, P. G.; Cecconi, I.; Leverenz, V.; Giblin, F. J.; Del Corso, A.; Mura, U. Occurrence of Glutathione-Modified Aldose Reductase in Oxidatively Stressed Bovine Lens Biochem. Biophys. Res. Commun. 1995, 207, 775-782
103. Muthenna, P.; Suryanarayana, P.; Gunda, S. K.; Petrash, J. M.; Reddy, G. B. Inhibition of Aldose Reductase by Dietary Antioxidant Curcumin: Mechanism of Inhibition, Specificity and Significance FEBS Lett. 2009, 583, 3637-3642
104. Berrone, E.; Beltramo, E.; Solimine, C.; Ubertalli Ape, A.; Porta, M. Regulation of Intracellular Glucose and Polyol Pathway by Thiamine and Benfotiamine in Vascular Cells Cultured in High Glucose J. Biol. Chem. 2006, 281, 9307-9313
105. Kanazu, T.; Shinoda, M.; Nakayama, T.; Deyashiki, Y.; Hara, A.; Sawada, H. Aldehyde Reductase Is a Major Protein Associated with 3-Deoxyglucosone Reductase Activity in Rat, Pig, and Human Livers Biochem. J. 1991, 279, 903-906
106. Oya, T.; Hattori, N.; Mizuno, Y.; Miyata, S.; Maeda, S.; Osawa, T.; Uchida, K. Methylglyoxal Modification of Protein. Chemical and Immunochemical Characterization of Methylglyoxal-Arginine Adducts J. Biol. Chem. 1999, 274, 18492-18502
107. El-Kabbani, O.; Wilson, D. K.; Petrash, J. M.; Quiocho, F. A. Structural Features of the Aldose Reductase and Aldehyde Reductase Inhibitor-Binding Sites Mol. Vision 1998, 4, 19-25
108. El-Kabbani, O.; Podjarny, A. Selectivity Determinants of the Aldose and Aldehyde Reductase Inhibitor-Binding Sites Cell. Mol. Life Sci. 2007, 64, 1970-1978
109. El-Kabbani, O.; Darmanin, C.; Oka, M.; Schulze-Briese, C.; Tomizaki, T.; Hazemann, I.; Mitschler, A.; Podjarny, A. High-Resolution Structures of Human Aldose Reductase Holoenzyme in Complex with Stereoisomers of the Potent Inhibitor Fidarestat: Stereospecific Interaction between the Enzyme and a Cyclic Imide Type Inhibitor J. Med. Chem. 2004, 47, 4530-4537
110. El-Kabbani, O.; Carbone, V.; Darmanin, C.; Oka, M.; Mitschler, A.; Podjarny, A.; Schulze-Briese, C.; Chung, R. P.-T. Structure of Aldehyde Reductase Holoenzyme in Complex with the Potent Aldose Reductase Inhibitor Fidarestat: Implications for Inhibitor Binding and Selectivity J. Med. Chem. 2005, 48, 5536-5542
111. Petrova, T.; Steuber, H.; Hazemann, I.; Cousido-Siah, A.; Mitschler, A.; Chung, R.; Oka, M.; Klebe, G.; El-Kabbani, O.; Joachimiak, A.; Podjarny, A. Factorizing Selectivity Determinants of Inhibitor Binding toward Aldose and Aldehyde Reductases: Structural and Thermodynamic Properties of the Aldose Reductase Mutant Leu300Pro-Fidarestat Complex J. Med. Chem. 2005, 48, 5659-5665
112. Van Zandt, M. C.; Sibley, E. O.; McCann, E. E.; Combs, K. J.; Flam, B.; Sawicki, D. R.; Sabetta, A.; Carrington, A.; Sredy, J.; Howard, E.; Mitschler, A.; Podjarny, A. D. Design and Synthesis of Highly Potent and Selective (2-Arylcarbamoyl-phenoxy)-acetic Acid Inhibitors of Aldose Reductase for Treatment of Chronic Diabetic Complications Bioorg. Med. Chem. 2004, 12, 5661-5675
113. Podjarny, A.; Cachau, R. E.; Schneider, T.; Van Zandt, M.; Joachimiak, A. Subatomic and Atomic Crystallographic Studies of Aldose Reductase: Implications for Inhibitor Binding Cell. Mol. Life Sci. 2004, 61, 763-773
114. Howard, E. I.; Sanishvili, R.; Cachau, R. E.; Mitschler, A.; Chevrier, B.; Barth, P.; Lamour, V.; Van Zandt, M.; Sibley, E.; Bon, C.; Moras, D.; Schneider, T. R.; Joachimiak, A.; Podjarny, A. Ultrahigh Resolution Drug Design I: Details of Interactions in Human Aldose Reductase-Inhibitor Complex at 0.66 Å Proteins 2004, 55, 792-804
115. Van Zandt, M. C.; Jones, M. L.; Gunn, D. E.; Geraci, L. S.; Jones, J. H.; Sawicki, D. R.; Sredy, J.; Jacot, J. L.; DiCioccio, A. T.; Petrova, T.; Mitschler, A.; Podjarny, A. D. Discovery of 3-[(4,5,7-Trifluorobenzothiazol-2-yl)methyl]indole-N-acetic Acid (Lidorestat) and Congeners as Highly Potent and Selective Inhibitors of Aldose Reductase for Treatment of Chronic Diabetic Complications J. Med. Chem. 2005, 48, 3141-3152
116. Van Zandt, M. C.; Doan, B.; Sawicki, D. R.; Sredy, J.; Podjarny, A. D. Discovery of [3-(4,5,7-Trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b ]pyridin-1-yl]acetic Acids as Highly Potent and Selective Inhibitors of Aldose Reductase for Treatment of Chronic Diabetic Complications Bioorg. Med. Chem. Lett. 2009, 19, 2006-2008
117. Chen, X.; Zhu, C.; Guo, F.; Qiu, X.; Yang, Y.; Zhang, S.; He, M.; Parveen, S.; Jing, C.; Li, Y.; Ma, B. Acetic Acid Derivatives of 3,4-Dihydro-2 H-1,2,4-benzothiadiazine 1,1-Dioxide as a Novel Class of Potent Aldose Reductase Inhibitors J. Med. Chem. 2010, 53, 8330-8344
118. Zhang, S.; Chen, X.; Parveen, S.; Hussain, S.; Yang, Y.; Jing, C.; Zhu, C. Effect of C7 Modifications on Benzothiadiazine-1,1-dioxide Derivatives on Their Inhibitory Activity and Selectivity toward Aldose Reductase ChemMedChem 2013, 8, 603-613
119. Chen, X.; Yang, Y.; Ma, B.; Zhang, S.; He, M.; Gui, D.; Hussain, S.; Jing, C.; Zhu, C.; Yu, Q.; Liu, Y. Design and Synthesis of Potent and Selective Aldose Reductase Inhibitors Based on Pyridylthiadiazine Scaffold Eur. J. Med. Chem. 2011, 46, 1536-1544
120. Da Settimo, F.; Primofiore, G.; La Motta, C.; Sartini, S.; Taliani, S.; Simorini, F.; Marini, A. M.; Lavecchia, A.; Novellino, E.; Boldrini, E. Naphtho[1,2-d ]isothiazole Acetic Acid Derivatives as a Novel Class of Selective Aldose Reductase Inhibitors J. Med. Chem. 2005, 48, 6897-6907
121. Steuber, H.; Zentgraf, M.; La Motta, C.; Sartini, S.; Heine, A.; Klebe, G. Evidence for a Novel Binding Site Conformer of Aldose Reductase in Ligand-Bound State J. Mol. Biol. 2007, 369, 186-197
122. Zentgraf, M.; Steuber, H.; Koch, C.; La Motta, C.; Sartini, S.; Sotriffer, C. A.; Klebe, G. How Reliable Are Current Docking Approaches for Structure-Based Drug Design? Lessons from Aldose Reductase Angew. Chem., Int. Ed. 2007, 46, 3575-3578
123. La Motta, C.; Sartini, S.; Salerno, S.; Simorini, F.; Taliani, S.; Marini, A. M.; Da Settimo, F.; Marinelli, L.; Limongelli, V.; Novellino, E. Acetic Acid Aldose Reductase Inhibitors Bearing a Five-Membered Heterocyclic Core with Potent Topical Activity in a Visual Impairment Rat Model J. Med. Chem. 2008, 51, 3182-3193
124. Maccari, R.; Ottanà, R.; Ciurleo, R.; Vigorita, M. G.; Rakowitz, D.; Steindl, T.; Langer, T. Evaluation of In Vitro Aldose Reductase Inhibitory Activity of 5-Arylidene-2,4-thiazolidinediones Bioorg. Med. Chem. Lett. 2007, 17, 3886-3893
125. Carbone, V.; Giglio, M.; Chung, R.; Huyton, T.; Adams, J.; Maccari, R.; Ottanà, R.; Hara, A.; El-Kabbani, O. Structure of Aldehyde Reductase in Ternary Complex with a 5-Arylidene-2,4-thiazolidinedione Aldose Reductase Inhibitor Eur. J. Med. Chem. 2010, 45, 1140-1145
126. Puppala, M.; Ponder, J.; Suryanarayana, P.; Reddy, G. B.; Petrash, J. M.; LaBarbera, D. V. The Isolation and Characterization of β-Glucogallin as a Novel Aldose Reductase Inhibitor from Emblica officinalis PLoS ONE 2012, 7, e31399 10.1371/journal.pone.0031399
127. Wang, L.; Gu, Q.; Zheng, X.; Ye, J.; Liu, Z.; Li, J.; Hu, X.; Hagler, A.; Xu, J. Discovery of New Selective Human Aldose Reductase Inhibitors through Virtual Screening Multiple Binding Pocket Conformations J. Chem. Inf. Model. 2013, 53, 2409-2422
128. Ramunno, A.; Cosconati, S.; Sartini, S.; Maglio, V.; Angiuoli, S.; La Pietra, V.; Di Maro, S.; Giustiniano, M.; La Motta, C.; Da Settimo, F.; Marinelli, L.; Novellino, E. Progresses in the Pursuit of Aldose Reductase Inhibitors: The Structure-Based Lead Optimization Step Eur. J. Med. Chem. 2012, 51, 216-226
129. Minehira, D.; Takeda, D.; Urata, H.; Kato, A.; Adachi, I.; Wang, X.; Matsuya, Y.; Sugimoto, K.; Takemura, M.; Endo, S.; Matsunaga, T.; Hara, A.; Koseki, J.; Narukawa, K.; Hirono, S.; Toyooka, N. Design, Synthesis, and Biological Evaluation of Novel (1-Thioxo-1,2,3,4-tetrahydro-β-carbolin-9-yl)acetic Acids as Selective Inhibitors for AKR1B1 Bioorg. Med. Chem. 2012, 20, 356-367
130. Li, L.; Chang, K.-C.; Zhou, Y.; Shieh, B.; Ponder, J.; Abraham, A. D.; Ali, H.; Snow, A.; Petrash, J. M.; LaBarbera, D. V. Design of an Amide N-Glycoside Derivative of β-Glucogallin: A Stable, Potent, and Specific Inhibitor of Aldose Reductase J. Med. Chem. 2014, 57, 71-77
131. Martin, H. J.; Maser, E. Role of Human Aldo-Keto-Reductase AKR1B10 in the Protection against Toxic Aldehydes Chem.-Biol. Interact. 2009, 178, 145-150
132. Crosas, B.; Hyndman, D. J.; Gallego, O.; Martras, S.; Parés, X.; Flynn, T. G.; Farrés, J. Human Aldose Reductase and Human Small Intestine Aldose Reductase Are Efficient Retinal Reductases: Consequences for Retinoid Metabolism Biochem. J. 2003, 373, 973-979
133. Endo, S.; Matsunaga, T.; Mamiya, H.; Ohta, C.; Soda, M.; Kitade, Y.; Tajima, K.; Zhao, H.-T.; El-Kabbani, O.; Hara, A. Kinetic Studies of AKR1B10, Human Aldose Reductase-like Protein: Endogenous Substrates and Inhibition by Steroids Arch. Biochem. Biophys. 2009, 487, 1-9
134. Zhong, L.; Shen, H.; Huang, C.; Jing, H.; Cao, D. AKR1B10 Induces Cell Resistance to Daunorubicin and Idarubicin by Reducing C13 Ketonic Group Toxicol. Appl. Pharmacol. 2011, 255, 40-47
135. Endo, S.; Matsunaga, T.; Soda, M.; Tajima, K.; Zhao, H. T.; El-Kabbani, O.; Hara, A. Selective Inhibition of the Tumor Marker AKR1B10 by Antiinflammatory N-Phenylanthranilic Acids and Glycyrrhetic Acid Biol. Pharm. Bull. 2010, 33, 886-890
136. Matsunaga, T.; Endo, S.; Soda, M.; Zhao, H.-T.; El-Kabbani, O.; Tajima, K.; Hara, A. Potent and Selective Inhibition of the Tumor Marker AKR1B10 by Bisdemethoxycurcumin: Probing the Active Site of the Enzyme with Molecular Modeling and Site-Directed Mutagenesis Biochem. Biophys. Res. Commun. 2009, 389, 128-132
137. Zhao, H.-T.; Soda, M.; Endo, S.; Hara, A.; El-Kabbani, O. Selectivity Determinants of Inhibitor Binding to the Tumour Marker Human Aldose Reductase-like Protein (AKR1B10) Discovered from Molecular Docking and Database Screening Eur. J. Med. Chem. 2010, 45, 4354-4357
138. Endo, S.; Matsunaga, T.; Kuwata, K.; Zhao, H.-T.; El-Kabbani, O.; Kitade, Y.; Hara, A. Chromene-3-carboxamide Derivatives Discovered from Virtual Screening as Potent Inhibitors of the Tumour Maker, AKR1B10 Bioorg. Med. Chem. 2010, 18, 2485-2490
139. Takemura, M.; Endo, S.; Matsunaga, T.; Soda, M.; Zhao, H.-T.; El-Kabbani, O.; Tajima, K.; Iinuma, M.; Hara, A. Selective Inhibition of the Tumor Marker Aldo-Keto Reductase Family Member 1B10 by Oleanolic Acid J. Nat. Prod. 2011, 74, 1201-1206
140. Soda, M.; Hu, D.; Endo, S.; Takemura, M.; Li, J.; Wada, R.; Ifuku, S.; Zhao, H.-T.; El-Kabbani, O.; Ohta, S.; Yamamura, K.; Toyooka, N.; Hara, A.; Matsunaga, T. Design, Synthesis and Evaluation of Caffeic Acid Phenethyl Ester-Based Inhibitors Targeting a Selectivity Pocket in the Active Site of Human Aldo-Keto Reductase 1B10 Eur. J. Med. Chem. 2012, 48, 321-329
141. Ruiz, F. X.; Cousido-Siah, A.; Mitschler, A.; Farrés, J.; Parés, X.; Podjarny, A. X-ray Structure of the V301L Aldo-Keto Reductase 1B10 Complexed with NADP+ and the Potent Aldose Reductase Inhibitor Fidarestat: Implications for Inhibitor Binding and Selectivity Chem.-Biol. Interact. 2013, 202, 178-185
142. Zhang, L.; Zhang, H.; Zhao, Y.; Li, Z.; Chen, S.; Zhai, J.; Chen, Y.; Xie, W.; Wang, Z.; Li, Q.; Zheng, X.; Hu, X. Inhibitor Selectivity between Aldo-Keto Reductase Superfamily Members AKR1B10 and AKR1B1: Role of Trp112 (Trp111) FEBS Lett. 2013, 587, 3681-3686
143. Zheng, X.; Zhang, L.; Chen, W.; Chen, Y.; Xie, W.; Hu, X. Partial Inhibition of Aldose Reductase by Nitazoxanide and Its Molecular Basis ChemMedChem 2012, 7, 1921-1923
144. Kumar, H.; Shah, A.; Sobhia, M. E. Novel Insights into the Structural Requirements for the Design of Selective and Specific Aldose Reductase Inhibitors J. Mol. Model. 2012, 18, 1791-1799
145. Del Corso, A.; Balestri, F.; Di Bugno, E.; Moschini, R.; Cappiello, M.; Sartini, S.; La Motta, C.; Da Settimo, F.; Mura, U. A New Approach To Control the Enigmatic Activity of Aldose Reductase PLoS One 2013, 8, e74076 10.1371/journal.pone.0074076
146. Kim, Y. S.; Kim, N. H.; Jung, D. H.; Jang, D. S.; Lee, Y. M.; Kim, J. M.; Kim, J. S. Genistein Inhibits Aldose Reductase Activity and High Glucose-Induced TGF-β2 Expression in Human Lens Epithelial Cells Eur. J. Pharmacol. 2008, 594, 18-25
147. La Motta, C.; Sartini, S.; Mugnaini, L.; Simorini, F.; Taliani, S.; Salerno, S.; Marini, A. M.; Da Settimo, F.; Lavecchia, A.; Novellino, E.; Cantore, M.; Failli, P.; Ciuffi, M. Pyrido[1,2-a ]pyrimidin-4-one Derivatives as a Novel Class of Selective Aldose Reductase. Inhibitors Exhibiting Antioxidant Activity J. Med. Chem. 2007, 50, 4917-4927
148. Stefek, M.; Snirc, V.; Djoubissie, P.-O.; Majekova, M.; Demopoulos, V.; Rackova, L.; Bezakova, Z.; Karasu, C.; Carbone, V.; El-Kabbani, O. Carboxymethylated Pyridoindole Antioxidants as Aldose Reductase Inhibitors: Synthesis, Activity, Partitioning, and Molecular Modeling Bioorg. Med. Chem. 2008, 16, 4908-4920
149. Sartini, S.; Cosconati, S.; Marinelli, L.; Barresi, E.; Di Maro, S.; Simorini, F.; Taliani, S.; Salerno, S.; Marini, A. M.; Da Settimo, F.; Novellino, E.; La Motta, C. Benzofuroxane Derivatives as Multi-Effective Agents for the Treatment of Cardiovascular Diabetic Complications. Synthesis, Functional Evaluation, and Molecular Modeling Studies J. Med. Chem. 2012, 55, 10523-10531
150. Ottanà, R.; Maccari, R.; Giglio, M.; Del Corso, A.; Cappiello, M.; Mura, U.; Cosconati, S.; Marinelli, L.; Novellino, E.; Sartini, S.; La Motta, C.; Da Settimo, F. Identification of 5-Arylidene-4-thiazolidinone Derivatives Endowed with Dual Activity as Aldose Reductase Inhibitors and Antioxidant Agents for the Treatment of Diabetic Complications Eur. J. Med. Chem. 2011, 46, 2797-2806
151. Mylari, B. L.; Armento, S. J.; Beebe, D. A.; Conn, E. L.; Coutcher, J. B.; Dina, M. S.; O'Gorman, M. T.; Linhares, M. C.; Martin, W. H.; Oates, P. J.; Tess, D. A.; Withbroe, G. J.; Zembrowski, W. J. A Highly Selective, Non-Hydantoin, Non-Carboxylic Acid Inhibitor of Aldose Reductase with Potent Oral Activity in Diabetic Rat Models: 6-(5-Chloro-3-methylbenzofuran-2-sulfonyl)-2-H-pyridazin-3-one J. Med. Chem. 2003, 46, 2283-2286
152. Mylari, B. L.; Armento, S. J.; Beebe, D. A.; Conn, E. L.; Coutcher, J. B.; Dina, M. S.; O'Gorman, M. T.; Linhares, M. C.; Martin, W. H.; Oates, P. J.; Tess, D. A.; Withbroe, G. J.; Zembrowski, W. J. A Novel Series of Non-Carboxylic Acid, Non-Hydantoin Inhibitors of Aldose Reductase with Potent Oral Activity in Diabetic Rat Models: 6-(5-Chloro-3-methylbenzofuran-2-sulfonyl)-2 H-pyridazin-3-one and Congeners J. Med. Chem. 2005, 48, 6326-6339
153. Sun, W.; Oates, P. J.; Coutcher, J. B.; Gerhardinger, C.; Lorenzi, M. A Selective Aldose Reductase Inhibitor of a New Structural Class Prevents or Reverses Early Retinal Abnormalities in Experimental Diabetic Retinopathy Diabetes 2006, 55, 2757-2762
154. Steuber, H.; Zentgraf, M.; Podjarny, S.; Heine, A.; Klebe, G. High-Resolution Crystal Structure of Aldose Reductase with the Novel Sulfonyl-Pyridazinone Inhibitor Exhibiting an Alternative Active Site Anchoring Group J. Mol. Biol. 2006, 356, 45-56
155. Fresneau, P.; Cussac, M.; Morand, J. M.; Szymonski, B.; Tranqui, D.; Leclerc, G. Synthesis, Activity, and Molecular Modeling of New 2,4-Dioxo-5-(naphthylmethylene)-3-thiazolidineacetic Acids and 2-Thioxo Analogues as Potent Aldose Reductase Inhibitors J. Med. Chem. 1998, 41, 4706-4715
156. Maccari, R.; Del Corso, A.; Giglio, M.; Moschini, R.; Mura, U.; Ottanà, R. In vitro Evaluation of 5-Arylidene-2-thioxo-4-thiazolidinones Active as Aldose Reductase Inhibitors Bioorg. Med. Chem. Lett. 2011, 21, 200-203
157. Ali, S.; Saeed, A.; Abbas, N.; Shahid, M.; Bolte, M.; Iqbal, J. Design, Synthesis and Molecular Modelling of Novel Methyl[4-oxo-2-(aroylimino)-3-(substituted phenyl)thiazolidin-5-ylidene]acetates as Potent and Selective Aldose Reductase Inhibitors Med. Chem. Commun. 2012, 3, 1428-1434
158. Alexiou, P.; Nicolaou, I.; Stefek, M.; Kristl, A.; Demopoulos, V. J. Design and Synthesis of N-(3,5-Difluoro-4-hydroxyphenyl)benzenesulfonamides as Aldose Reductase Inhibitors Bioorg. Med. Chem. 2008, 16, 3926-3932
159. Alexiou, P.; Demopoulos, V. J. A Diverse Series of Substituted Benzenesulfonamides as Aldose Reductase Inhibitors with Antioxidant Activity: Design, Synthesis, and in Vitro Activity J. Med. Chem. 2010, 53, 7756-7766
160. Chatzopoulou, M.; Mamadou, E.; Juskova, M.; Koukoulitsa, C.; Nicolaou, I.; Stefek, M.; Demopoulos, V. J. Structure-Activity Relations on [1-(3,5-Difluoro-4-hydroxyphenyl)-1 H-pyrrol-3-yl]phenylmethanone. The Effect of Methoxy Substitution on Aldose Reductase Inhibitory Activity and Selectivity Bioorg. Med. Chem. 2011, 19, 1426-1433
161. Kotsampasakou, E.; Demopoulos, V. J. Synthesis of Derivatives of the Keto-pyrrolyl-difluorophenol Scaffold: Some Structural Aspects for Aldose Reductase Inhibitory Activity and Selectivity Bioorg. Med. Chem. 2013, 21, 869-873
162. Pegklidou, K.; Koukoulitsa, C.; Nicolaou, I.; Demopoulos, V. J. Design and Synthesis of Novel Series of Pyrrole Based Chemotypes and Their Evaluation as Selective Aldose Reductase Inhibitors. A Case of Bioisosterism between a Carboxylic Acid Moiety and That of a Tetrazole Bioorg. Med. Chem. 2010, 18, 2107-2114
163. Papastavrou, N.; Chatzopoulou, M.; Pegklidou, K.; Nicolaou, I. 1-Hydroxypyrazole as a Bioisostere of the Acetic Acid Moiety in a Series of Aldose Reductase Inhibitors Bioorg. Med. Chem. 2013, 21, 4951-4957
164. Chatzopoulou, M.; Patsilinakos, A.; Vallianatou, T.; Prnova, M. S.; Zakelj, S.; Ragno, R.; Stefek, M.; Kristl, A.; Tsantili-Kakoulidou, A.; Demopoulos, V. J. Decreasing Acidity in a Series of Aldose Reductase Inhibitors: 2-Fluoro-4-(1 H-pyrrol-1-yl)phenol as a Scaffold for Improved Membrane Permeation Bioorg. Med. Chem. 2014, 22, 2194-2207
165. Maccari, R.; Ottanà, R.; Ciurleo, R.; Rakowitz, D.; Matuszczak, B.; Laggner, C.; Langer, T. Synthesis, Induced-Fit Docking Investigations, and in Vitro Aldose Reductase Inhibitory Activity of Non-Carboxylic Acid Containing 2,4-Thiazolidinedione Derivatives Bioorg. Med. Chem. 2008, 16, 5840-5852
166. Maccari, R.; Ciurleo, R.; Giglio, M.; Cappiello, M.; Moschini, R.; Del Corso, A.; Mura, U.; Ottanà, R. Identification of New Non-Carboxylic Acid Containing Inhibitors of Aldose Reductase Bioorg. Med. Chem. 2010, 18, 4049-4055
167. Cosconati, S.; Marinelli, L.; La Motta, C.; Sartini, S.; Da Settimo, F.; Olson, A. J.; Novellino, E. Pursuing Aldose Reductase Inhibitors through in Situ Cross-Docking and Similarity-Based Virtual Screening J. Med. Chem. 2009, 52, 5578-5581