A Molecular Docking and Pharmacokinetic Prediction of Thiazolidine-2, 4-dione Derivatives: Toward Novel Therapeutic Targets for Type-2 Diabetes Mellitus

Pradeep Tiwari, Renuka Suravajhala, Sonal Gupta, Pragya Chaturvedi, Sandeep Kumar Mathur, Pooran Singh Solanki, Babita Malik

Abstract


Type 2 diabetes mellitus (T2DM) is a leading endocrine disorder that affects millions of people worldwide. It is characterized by hyperglycemia and high insulin resistance. The commonly prescribed oral therapeutic for insulin resistance in T2DM is Thiazolidine-2, 4-diones (TZDs). TZDs are a class of oral hypoglycemic agents that act on Peroxisome proliferator activating receptor-γ (PPAR-γ) receptors and are mainly expressed in the adipose tissues. In this work, we derive novel classes of TZDs and predict the nature of structural affinity using docking studies against the PPAR-γ. 

Full Text:

PDF

References


Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010; 87:4–14.

Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res. Clin. Pract. 2011; 94: 311-21.

Taylor R. Insulin Resistance and Type 2 Diabetes. Diabetes. 2012; 61:778–779.

Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006; 444: 840-6.

Lambadiari V, Triantafyllou K, Dimitriadis GD. Insulin action in muscle and adipose tissue in type 2 diabetes: The significance of blood flow. World J Diabetes. 2015; 6: 626–633.

Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs. 2005; 65:385-411.

Marín-Peñalver JJ, Martín-Timón I, Sevillano-Collantes C, Cañizo-Gómez FJ. Update on the treatment of type 2 diabetes mellitus. World J Diabetes. 2016; 7: 354–395.

Israili ZH Advances in the treatment of type 2 diabetes mellitus. Am J Ther. 2011; 18: 117-52.

Nyenwe EA, Jerkins TW, Umpierrez GE, Kitabchia AE. Management of type 2 diabetes: evolving strategies for the treatment of patients with type 2 diabetes. Metabolism. 2011; 60: 1–23.

Chaudhury A, Duvoor C, Dendi VSR, Kraleti S, Chada A, Ravilla R, Marco A, Shekhawat NS, Montales MT, Kuriakose K, Sasapu A, Beebe A, Patil N, Musham CK, Lohani GP, Mirza W . Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management. Front Endocrinol (Lausanne) 2017; 8:6.

Edelman SV. Type II diabetes mellitus. Adv Intern Med. 1998; 43:449-500.

Yki-Järvinen H . Thiazolidinediones. New Eng J Med. 2004; 351:1006.

Desai NC, Pandit UP, Dodiya A . Thiazolidinedione compounds: patent review (2010 - present). Expert Opin Ther Pat. 2015; 25:479-88.

Chadha N, Bahia MS, Kaur M, Silakari O. Thiazolidine-2,4-dione derivatives: programmed chemical weapons for key protein targets of various pathological conditions. Bioorg Med Chem. 2015; 23:2953-74.

Cabrero A, Laguna JC, Vazquez M. Peroxisome proliferator activated receptors and the control of inflammation. Curr Drug Targets Inflamm Allergy. 2002; 1:243-8.

Saltiel AR, Olefsky JM .Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes. 1996; 45: 1661-9.

Diamant M, Heine RJ. Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence. Drugs.2003; 63: 1373-405.

Hauner H. The mode of action of thiazolidinediones. Diabetes Metab Res Rev. 2002; 18: S10-5.

Capelli D, Cerchia C, Montanari R, Loiodice F, Tortorella P, Laghezza A, Lavecchia A. Structural basis for PPAR partial or full activation revealed by a novel ligand binding mode. Sci Rep. 2016; 6: 34792.

Chen Y, Hu Y, Lin M, Jenkins AJ, Keech AC, Mott R, Lyons TJ, Ma JX. Therapeutic effects of PPARα agonists on diabetic retinopathy in type 1 diabetes models. Diabetes. 2013; 62: 261-72.

Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M, Evans RM. PPARγ signaling and metabolism: the good, the bad and the future. Nat Med. 2013; 19: 557-66.

Chui PC, Guan HP, Lehrke M, Lazar MA. PPARγ regulates adipocyte cholesterol metabolism via oxidized LDL receptor. J Clin Invest. 2005; 115: 2244-56.

Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature. 2000; 405: 421-4.

Stienstra R, Duval C, Müller M, Kersten S. PPARs, Obesity, and Inflammation. PPAR Res. 2007; 95974.

Youssef J, Badr M. Role of Peroxisome Proliferator-Activated Receptors in Inflammation Control. J Biomed Biotechnol. 2004; 156:16.

Kapadia R, Yi JH, Vemuganti R. Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists. Front Biosci. 2008; 13:1813-26.

Shah P, Mudaliar S. Pioglitazone: side effect and safety profile. Expert Opin Drug Saf. 2010; 9:347-54.

Rizos CV, Elisaf MS, Mikhailidis DP, Liberopoulos EN. How safe is the use of thiazolidinediones in clinical practice? Expert Opin Drug Saf. 2009; 8:15-32.

Scheen AJ .Thiazolidinediones and liver toxicity. Diabetes Metab. 2001; 27: 305-13.

Kung J, Henry RR. Thiazolidinedione safety. Expert Opin Drug Saf. 2012; 11: 565-79.

Kokil GR, Veedu RN, Ramm GA, Prins JB, Parekh HS. Type 2 diabetes mellitus: limitations of conventional therapies and intervention with nucleic acid-based therapeutics. Chem Rev. 2015; 115: 4719-43.

Yasmin S, Capone F, Laghezza A, Piaz FD, Loiodice F, Lavecchia A. Novel Benzylidene Thiazolidinedione Derivatives as Partial PPARγ Agonists and their Antidiabetic Effects on Type 2 Diabetes. Sci Rep. 2017; 7: 14453.

Ye J. Challenges in Drug Discovery for Thiazolidinedione Substitute. Yao Xue Xue Bao. 2011; 1:137–142.

Boubia B, Poupardin O, Barth M, Binet J, Peralba P, Mounier L, et al. Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) α/γ/δ Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate. J Med Chem. 2018; 61: 2246-2265.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. Nucleic Acids Res. 2000; 28: 235-42.

Hughes TS, Giri PK, Vera IM, Marciano DP, Kuruvilla DS, Shin Y, Douglas J, Kojetin DJ. An alternate binding site for PPARg ligands. Nature Communications. 2014; 5: 3571.

Lee MA, Tan L, Yang H, Im YG, Im YJ. Structures of PPARγ complexed with lobeglitazone and pioglitazone reveal key determinants for the recognition of antidiabetic drugs. Sci Rep. 2017; 7: 16837.

Schwede T, Kopp J, Guex N, Peitsch MC. SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Res. 2003; 31: 3381-5.

Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 2018; 46: W296-W303.

Morris GM, Goodsell, DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ. Automated Docking Using a Lamarckian Genetic Algorithm and Empirical Binding Free Energy Function J. Computational Chemistry 1998; 19: 1639-1662.

Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G. admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model. 2012; 52: 3099-105.

Grosdidier A, Zoete V, Michielin O. SwissDock, a protein-small molecule docking web service based on EADock DSS. Nucleic Acids Res. 2011; 39: W270-7.

Tiwari P, Saxena A, Gupta N, Medicherla KM, Suravajhala P and Mathur SK. Systems Genomics of Thigh Adipose Tissue from Asian Indian Type-2 Diabetics Revealed Distinct Protein Interaction Hubs. Front. Genet. 2018; 9: 00679.| doi: 10.3389/fgene.2018.00679.