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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Review Article

2,4-Thiazolidinediones as PTP 1B Inhibitors: A Mini Review (2012-2018)

Author(s): Sant Kumar Verma, Yatesh Sharad Yadav and Suresh Thareja*

Volume 19, Issue 7, 2019

Page: [591 - 598] Pages: 8

DOI: 10.2174/1389557518666181026092029

Price: $65

Abstract

2,4-thiazolidinedione (TZD) scaffold is a synthetic versatile scaffold explored by medicinal chemists for the discovery of novel molecules for the target-specific approach to treat or manage number of deadly ailments. PTP 1B is the negative regulator of insulin signaling cascade, and its diminished activity results in abolishment of insulin resistance associated with T2DM. The present review focused on the seven years journey (2012-2018) of TZDs as PTP 1B inhibitors with the insight into the amendments in the structural framework of TZD scaffold in order to optimize/design potential PTP 1B inhibitors. We have investigated the synthesized molecules based on TZD scaffold with potential activity profile against PTP 1B. Based on the SAR studies, the combined essential pharmacophoric features of selective and potent TZDs have been mapped and presented herewith for further design and synthesis of novel inhibitors of PTP 1B. Compound 46 bearing TZD scaffold with N-methyl benzoic acid and 5-(3-methoxy-4-phenethoxy) benzylidene exhibited the most potent activity (IC50 1.1 µM). Imidazolidine-2,4-dione, isosteric analogue of TZD, substituted with 1-(2,4-dichlorobenzyl)-5-(3-(2,4- dichlorobenzyloxy)benzylidene) (Compound 15) also endowed with very good PTP inhibitory activity profile (IC50 0.57 µM). It is noteworthy that Z-configuration is essential in structural framework around the double bond of arylidene for the designing of bi-dentate ligands with optimum activity.

Keywords: Imidazolidinedione, insulin resistance, insulin signaling cascade, protein tyrosine phosphatase (PTP 1B), thiazolidinediones, type 2 diabetes mellitus (T2DM).

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[1]
Verma, S.K.; Thareja, S. Molecular docking assisted 3D-QSAR study of benzylidene-2, 4-thiazolidinedione derivatives as PTP-1B inhibitors for the management of type-2 diabetes mellitus. RSC Advances, 2016, 6, 33857-33867.
[2]
Arner, P. Insulin resistance in type 2 diabetes: Role of fatty acids. Diabetes Metab. Res. Rev., 2002, 18, S5-S9.
[3]
Saltiel, A.R.; Kahn, C.R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature, 2001, 414, 799-806.
[4]
Muoio, D.M.; Newgard, C.B. Molecular and metabolic mechanisms of insulin resistance and β‑cell failure in type 2 diabetes. Nat. Rev. Mol. Cell Biol., 2008, 9, 193-205.
[5]
Dandona, P.; Aljada, A.; Chaudhuri, A.; Bandyopadhyay, A. The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis-related complications in type 2 diabetes. J. Clin. Endocrinol. Metab., 2003, 88, 2422-2429.
[6]
Meshkania, R.; Adelib, K. Hepatic insulin resistance, metabolic syndrome and cardiovascular disease. Clin. Biochem., 2009, 42, 1331-1346.
[7]
Tanti, J.F.; Jager, J. Cellular mechanisms of insulin resistance: Role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation. Curr. Opin. Pharmacol., 2009, 9, 753-762.
[8]
Mackenzie, R.W.A.; Elliott, B.T. Akt/PKB activation and insulin signaling: A novel insulin signaling pathway in the treatment of type 2 diabetes. Diabetes Metab. Syndr. Obes., 2014, 7, 55-64.
[9]
Nigro, J.; Osman, N.; Dart, A.M.; Little, P.J. Insulin resistance and atherosclerosis. Endocr. Rev., 2006, 27, 242-259.
[10]
Thareja, S.; Verma, S.K.; Haksar, D.; Bhardwaj, T.R.; Kumar, M. Discovery of novel cinnamylidene-thiazolidinedione derivatives as PTP-1B inhibitors for the management of type 2 diabetes. RSC Advances, 2016, 6, 108928-108940.
[11]
IDF , Diabetes Atlas. . Eighth edition 2017: International Diabetes Federation https://www.idf.org/e-library/epidemiology-research/
diabetes-atlas/134-idf-diabetes-atlas-8th-edition.html (Assessed July 10, 2018)
[12]
Jaacks, L.M.; Siegel, K.R.; Gujral, U.P.; Narayan, K.M. Type 2 diabetes: A 21st century epidemic. Best Pract. Res. Clin. Endocrinol. Metab., 2016, 30, 331-343.
[13]
Jain, S. Saraf. S. Type 2 diabetes mellitus-Its global prevalence and therapeutic strategies. Diabetes Metab. Syndr.: Clin. Res. Rev., 2010, 4, 48-56.
[14]
Reinehr, T. Type 2 diabetes mellitus in children and adolescents. World J. Diabetes, 2013, 4, 270-281.
[15]
Amed, S.; Daneman, D.; Mahmud, F.H.; Hamilton, J. Type 2 diabetes in children and adolescents. Expert Rev. Cardiovasc. Ther., 2010, 8, 393-406.
[16]
Goran, M.I.; Ball, G.D.; Cruz, M.L. Obesity and Risk of type 2 diabetes and cardiovascular disease in children and adolescents, obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. J. Clin. Endocrinol. Metab., 2003, 88, 1417-1427.
[17]
Rewers, M.; Pihoker, C.; Donaghue, K.; Hanas, R.; Swift, P.; Klingensmith, G.J. Assessment and monitoring of glycemic control in children and adolescents with diabetes. Pediatr. Diabetes, 2009, 10, 71-81.
[18]
Jain, A.K.; Vaidya, A.; Ravichandran, V.; Kashaw, S.K.; Agrawal, R.K. Recent developments and biological activities of thiazolidinone derivatives: A review. Bioorg. Med. Chem., 2012, 20, 3378-3395.
[19]
Jain, V.S.; Vora, D.K.; Ramaa, C.S. Thiazolidine-2,4-diones: Progress towards multifarious applications. Bioorg. Med. Chem., 2013, 21, 1599-1620.
[20]
Naim, M.J.; Alam, M.J.; Ahmad, S.; Nawaz, F.; Shrivastava, N.; Sahu, M.; Alam, O. Therapeutic journey of 2,4-thiazolidinediones as a versatile scaffold: An insight into structure activity relationship. Eur. J. Med. Chem., 2017, 129, 218-250.
[21]
Nomura, M.; Kinoshita, S.; Satoh, H.; Maeda, T.; Murakami, K.; Tsunoda, M.; Miyachi, H.; Awano, K. (3-Substituted benzyl)thiazolidine-2,4-diones as structurally new antihyperglycemic agents. Bioorg. Med. Chem. Lett., 1999, 9, 533-538.
[22]
Kung, J.; Henry, R.R. Thiazolidinedione safety. Expert Opin. Drug Saf., 2012, 11, 565-579.
[23]
Hiatt, W.R.; Kaul, S.; Smith, R.J. The cardiovascular safety of diabetes drugs-insights from the rosiglitazone experience. N. Engl. J. Med., 2013, 369, 1285-1287.
[24]
Agrawal, R.; Jain, P.; Dikshit, S.N. Balaglitazone: A second generation peroxisome proliferator-activated receptor (PPAR) gamma (γ) agonist. Mini Rev. Med. Chem., 2012, 12, 87-97.
[25]
Thareja, S.; Aggarwal, S.; Bhardwaj, T.R.; Kumar, M. Protein tyrosine phosphatase 1B inhibitors: A molecular level legitimate approach for the management of diabetes mellitus. Med. Res. Rev., 2010, 32, 459-517.
[26]
Verma, S.K.; Rajpoot, T.; Gautam, M.K.; Jain, A.K.; Thareja, S. Design of novel biphenyl-2-thioxothiazolidin-4-one derivatives as potential protein tyrosine phosphatase (PTP)-1B inhibitors using molecular docking study. Lett. Drug Des. Discov., 2016, 13, 295-300.
[27]
Verma, S.K.; Thareja, S. Formylchromone derivatives as novel and selective PTP-1B inhibitors: A drug design aspect using molecular docking-based self-organizing molecular field analysis. Med. Chem. Res., 2016, 25, 1433-1467.
[28]
Zhang, S.; Zhang, Z.Y. PTP1B as a drug target: Recent developments in PTP 1B inhibitor discovery. Drug Discov. Today, 2007, 12, 373-381.
[29]
Koren, S.; Fantus, I.G. Inhibition of the protein tyrosine phosphatase PTP 1B: Potential therapy for obesity, insulin resistance and type-2 diabetes mellitus. Best Pract. Res. Clin. Endocrinol. Metab., 2007, 21, 621-640.
[30]
Zhang, Z.Y.; Lee, S.Y. PTP 1B inhibitors as potential therapeutics in the treatment of type 2 diabetes and obesity. Expert Opin. Investig. Drugs, 2003, 12, 223-233.
[31]
Moller, D.E. New drug targets for type 2 diabetes and the metabolic syndrome. Nature, 2001, 414, 821-827.
[32]
Swarbrick, M.M.; Havel, P.J.; Levin, A.A.; Bremer, A.A.; Stanhope, K.L.; Butler, M.; Booten, S.L.; Graham, J.L.; McKay, R.A.; Murray, S.F.; Watts, L.M.; Monia, B.P.; Bhanot, S. Inhibition of protein tyrosine phosphatase-1B with antisense oligonucleotides improves insulin sensitivity and increases adiponectin concentrations in monkeys. Endocrinology, 2009, 150, 1670-1679.
[33]
Rakse, M.; Karthikeyan, C.; Deora, G.S.; Moorthy, N.S.; Rathore, V.; Rawat, A.K.; Srivastava, A.K.; Trivedi, P. Design, synthesis and molecular modelling studies of novel 3-acetamido-4-methyl benzoic acid derivatives as inhibitors of protein tyrosine phosphatase 1B. Eur. J. Med. Chem., 2013, 70, 469-476.
[34]
Panzhinskiy, E.; Ren, J.; Nair, S. Pharmacological inhibition of protein tyrosine phosphatase 1B: A promising strategy for the treatment of obesity and type 2 diabetes mellitus. Curr. Med. Chem., 2013, 20, 2609-2625.
[35]
Bhattarai, B.R.; Kafle, B.; Hwang, J.S.; Ham, S.W.; Lee, K.H.; Park, H.; Han, I.O.; Cho, H. Novel thiazolidinedione derivatives with anti-obesity effects: Dual action as PTP1B inhibitors and PPAR-γ activators. Bioorg. Med. Chem. Lett., 2010, 20, 6758-6763.
[36]
Liu, J.Z.; Zhang, S.E.; Nie, F.; Yang, Y.; Tang, Y.B.; Yin, W.; Tian, J.Y.; Ye, F.; Xiao, Z. Discovery of novel PTP1B inhibitors via pharmacophore-oriented scaffold hopping from Ertiprotafib. Bioorg. Med. Chem. Lett., 2013, 23, 6217-6222.
[37]
Salmeen, A.; Andersen, J.N.; Myers, M.P.; Tonks, N.K.; Barford, D. Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B. Mol. Cell, 2000, 6, 1401-1412.
[38]
Zhang, Z.Y. Protein tyrosine phosphatases: Structure and function, substrate specificity, and inhibitor development. Annu. Rev. Pharmacol. Toxicol., 2002, •••, 42-, 209-234. [n].
[39]
Sarmiento, M.; Zhao, Y.; Gordon, S.J.; Zhang, Z.Y. Molecular basis for substrate specificity of protein-tyrosine phosphatase 1B. J. Biol. Chem., 1998, 273, 26368-26374.
[40]
Blaskovich, M.A. Drug discovery and protein tyrosine phosphatases. Curr. Med. Chem., 2009, 16, 2095-2176.
[41]
Tonks, N.K. Protein tyrosine phosphatases: From genes, to function, to disease. Nat. Rev. Mol. Cell Biol., 2006, 7, 833-846.
[42]
Dewang, P.M.; Hsu, N.M.; Peng, S.Z.; Li, W.R. Protein tyrosine phosphatases and their inhibitors. Curr. Med. Chem., 2005, 12, 1-22.
[43]
Taylor, S.D. Inhibitors of protein tyrosine phosphatase 1B (PTP1B). Curr. Top. Med. Chem., 2003, 3, 759-782.
[44]
Liu, Z.; Lee, W.; Kim, S.N.; Yoon, G.; Cheon, S.H. Design, synthesis, and evaluation of bromo-retrochalcone derivatives as protein tyrosine phosphatase 1B inhibitors. Bioorg. Med. Chem. Lett., 2011, 21, 3755-3758.
[45]
Wang, Z.; Liu, Z.; Lee, W.; Kim, S.N.; Yoon, G.; Cheon, S.H. Design, synthesis and docking study of 5-(substituted benzylidene)thiazolidine-2,4-dione derivatives as inhibitors of protein tyrosine phosphatase 1B. Bioorg. Med. Chem. Lett., 2014, 24, 3337-3340.
[46]
Ma, Y.; Sun, S.X.; Cheng, X.C.; Wang, S.Q.; Dong, W.L.; Wang, R.L.; Xu, W.R. Design and synthesis of imidazolidine-2,4-dione derivatives as selective inhibitors by targeting protein tyrosine phosphatase-1B over T-cell protein tyrosine phosphatase. Chem. Biol. Drug Des., 2013, 82, 595-602.
[47]
Voigt, J.H.; Bienfait, B.; Wang, S.; Nicklaus, M.C. Comparison of the NCI open database with seven large chemical structural databases. J. Chem. Inf. Comput. Sci., 2001, 41, 702-712.
[48]
Ma, Y.; Wang, S.Q.; Xu, W.R.; Wang, R.L.; Chou, K.C. Design novel dual agonists for treating type-2 diabetes by targeting peroxisome proliferator-activated receptors with core hopping approach. PLoS One, 2012, 7, e38546.
[49]
Wang, M.Y.; Jin, Y.Y.; Wei, H.Y.; Zhang, L.S.; Sun, S.X.; Chen, X.B.; Dong, W.L.; Xu, W.R.; Cheng, X.C.; Wang, R.L. Synthesis, biological evaluation and 3D-QSAR studies of imidazolidine-2,4-dione derivatives as novel protein tyrosine phosphatase 1B inhibitors. Eur. J. Med. Chem., 2015, 103, 91-104.
[50]
Thuan, N.T.; Dung, D.T.M.; Que, D.N.; Dung, P.T.P.; Vu, T.K.; Hahn, H.; Han, B.W.; Kim, Y.; Han, S.B.; Nam, N.H. Synthesis and bioevaluation of new 5-benzylidenethiazolidine-2,4-diones bearing benzenesulfonamide moiety. Med. Chem. Res., 2015, 24, 3803-3812.
[51]
Meng, G.; Zheng, M.; Wang, M.; Tong, J.; Ge, W.; Zhang, J.; Zheng, A.; Li, J.; Gao, L.; Li, J. Design and synthesis of new potent PTP1B inhibitors with the skeleton of 2-substituted imino-3-substituted-5-heteroarylidene-1,3-thiazolidine-4-one: part I. Eur. J. Med. Chem., 2016, 22, 756-769.
[52]
Mahapatra, M.K.; Kumar, R.; Kumar, M. Synthesis, biological evaluation and in silico studies of 5-(3-methoxybenzylidene) thiazolidine-2,4-dione analogues as PTP1B inhibitors. Bioorg. Chem., 2017, 71, 1-9.
[53]
Mahapatra, M.K.; Kumar, R.; Kumar, M. N-alkylated thiazolidine-2,4-dione analogs as PTP1B inhibitors: Synthesis, biological activity, and docking studies. Med. Chem. Res., 2017, 26, 1176-1183.
[54]
Mahapatra, M.K.; Kumar, R.; Kumar, M. Exploring sulfonate esters of 5-arylidene thiazolidine-2,4-diones as PTP 1B inhibitors with anti-hyperglycemic activity. Med. Chem. Res., 2018, 27, 476-487.
[55]
Ottana, R.; Maccari, R.; Amuso, S.; Wolber, G.; Schuster, D.; Herdlinger, S.; Manao, G.; Camici, G.; Paoli, P. New 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on mouse C2C12 skeletal muscle cells. Eur. J. Med. Chem., 2012, 50, 332-343.
[56]
Ottana, R.; Maccari, R.; Mortier, J.; Caselli, A.; Amuso, S.; Camici, G.; Rotondo, A.; Wolber, G.; Paoli, P. Synthesis, biological activity and structure activity relationships of new benzoic acid-based protein tyrosine phosphatase inhibitors endowed with insulinomimetic effects in mouse C2C12 skeletal muscle cells. Eur. J. Med. Chem., 2014, 71, 112-127.

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