Antihyperglycemic and Antihyperlipidemic Effects of Newly Synthesized Glibenclamide Analogues on Streptozotocin-diabetic Rats

A. Ahmadi; M. Khalili; M. Farsadrooh; M. Ghiasi; B. Nahri-Niknafs

doi:10.1055/s-0033-1349128

Drug Research, Table of Contents

Drug Res (Stuttg) 2013; 63(12): 614-619
DOI: 10.1055/s-0033-1349128

Original Article

Antihyperglycemic and Antihyperlipidemic Effects of Newly Synthesized Glibenclamide Analogues on Streptozotocin-diabetic Rats

Authors

A. Ahmadi

¹Department of Chemistry, Faculty of Science, Islamic Azad University, Karaj Branch, Karaj, Iran
M. Khalili

²Department of Physiology, Neuroscience and Herbal Medicine Research Center, Shahed University, Tehran, Iran
M. Farsadrooh

¹Department of Chemistry, Faculty of Science, Islamic Azad University, Karaj Branch, Karaj, Iran
M. Ghiasi

¹Department of Chemistry, Faculty of Science, Islamic Azad University, Karaj Branch, Karaj, Iran
B. Nahri-Niknafs

¹Department of Chemistry, Faculty of Science, Islamic Azad University, Karaj Branch, Karaj, Iran

Abstract

In this study, new glibenclamide analogues (5a–d) with substituted pharmacological triethoxysilyl propan, allyl and ethoxyphenyl groups for cyclohexyl moiety have been synthesized by condensing sulfonamide (4) with related isocyanate or isothiocyanate’s compounds. The newly synthesized drugs were evaluated for their antihyperglycemic and antihyperlipidemic activities with streptozotocin (STZ)-induced diabetic rats. All showed hypoglycemic and hypolipidemic activities compared to the control animals but 5c and 5d exhibited more and significant lowering blood activities similar to glibenclamide. This was concerned with identical affinities to bind with SUR1 receptor. Moreover, the new drugs displayed high efficiency for reducing serum LDL level which resulted in a high HDL/LDL ratio as a good lipid profile compared to other groups.

Key words

glibenclamide - sulfonylurea - antihyperglycemic - antihyperlipidemic activities

Full Text

References

References
1 Williams DA, Lemke TL. Foye’s principles of medicinal chemistry. 6^th ed. Philadelphia: Lippincott Williams & Wilkins; 2008
2 Nehlin JO. Recent developments in the treatment of diabetes type 2. Title book: Prevention and Treatment of Age-related Diseases, Rattan SIS, Kassem M. Springer; Netherlands: 2006: 133-157
3 Shingalapur RV, Hosamani KM, Keri RS et al. Derivatives of benzimidazole pharmacophore: Synthesis, anticonvulsant, antidiabetic and DNA cleavage studies. Eur J Med Chem 2010; 45: 1753-1759
4 Satoh J, Takahashi K, Takizawa Y et al. Secondary sulfonylurea failure: Comparison of period until insulin treatment between diabetic patients treated with gliclazide and Glibenclamide. Diabetes Res Clin Pract 2005; 70: 291-297
5 Jawale DV, Pratap UR, Rahuja N et al. Synthesis and antihyperglycemic evaluation of new 2,4 thiazolidinediones having biodynamic aryl sulfonylurea moieties. Bioorg Med Chem Lett 2012; 22: 436-439
6 Osei K, O’Dorisio TM, Falko JM. Concomitant Insulin and Sulfonylurea Therapy in Patients with Type II Diabetes Effects on Glucoregulation and Lipid Metabolism. Am J Med 1984; 77: 1002-1009
7 Matsui J, Ogawa Y, Tamasawa N et al. Comparison of the effects of glimepride and Glibenclamide on lipid metabolism in patients with type 2 diabetes. Poster Session. Pathophysiology of lipids and lipoproteins. XIV international Symposium on Atherosclerosis, Rome, Italy, 2006 Th-P15:61
8 Johannes P, Hans-Frieder K. BM 17.0744: A Structurally New Antidiabetic Compound with Insulin-Sensitizing and Lipid-Lowering Activity. Metabolism 1999; 48: 34-40
9 Howard BV, Xiaoren P, Harper I et al. Effect of sulfonylurea therapy on plasma lipids and high density lipoprotein composition in non-insulin-dependent diabetes mellitus. Am J Med 1985; 79: 78-85
10 Perfetti R, Ahmad A. Novel Sulfonylurea and Non-sulfonylurea Drugs to Promote the Secretion of Insulin. Trends Endocrinol Metab 2000; 11: 218-223
11 Zaman MK, Arayne MS, Sultana N et al. Synthesis and characterization of Glibenclamide complexes of magnesium, chromium, cobalt, nickel, zinc and cadmium salts. Pak J Pharm Sci 2006; 19: 114-118
12 Chambers J, Ames RS, Bergsma D et al. Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1. Nature 1999; 400: 261-265
13 Kim SH, Lee SB, Yoon SH et al. Assignee: LG Life Sciences Ltd. Glucokinase activators and pharmaceutical compositions containing the same as an active ingredient. United States Patent 2012 US 8,309,586
14 Ohyama S, Takano H, Iino T et al. A small-molecule glucokinase activator lowers blood glucose in the sulfonylurea-desensitized rat. Eur J Pharmacol 2010; 640: 250-256
15 Chester CY, Kevin Y, Simon Van Der P et al. Substituted aryl-amine derivatives and methods of use. Assignees: Amgen Inc. United States Patent 2009 US20090143355
16 Andrews RC, Ankersen M, Bloch P et al. Aryl carbonyl derivatives as therapeutic agents. Assignee: Novo Nordisk AS, European Patent 2012 EP 2471533 A1
17 Ahmadi A, Khalili M, Seyedhoseyni S et al. Synthesis, Antidiabetic and Hypolipidemic Activities of New Diethylamine and Triethoxysilyl Derivatives of Tolbutamide on Rats. Med Chem 2012; 8: 964-969
18 Patel SS, Shah RS, Goyal RK. Antihyperglycemic, antihyperlipidemic and antioxidant effects of Dihar, a polyherbal ayurvedic formulation in streptozotocin induced diabetic rats. Indian J Exp Biol 2009; 47: 564-570
19 Velingkar VS, Dandekar VD, Murugananthan K. Synthesis and pharmacological evaluation of some novel potent type II antidiabetic agents. Inter J Pharm Pharm Sci 2009; 149-158
20 Ceras J, Cirauqui N, Pérez-Silanes S et al. Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies. Eur J Med Chem 2012; 52: 1-13
21 Calderone V, Rapposelli S, Martelli A et al. No-Glibenclamide derivatives: Prototypes of a new class of nitric oxide-releasing antidiabetic drugs. Bioorg Med Chem 2009; 17: 5426-5432
22 Proks P, Reimann F, Green N et al. Sulfonylurea Stimulation of Insulin Secretion. Diabetes 2002; 51: S368-S376
23 Chakrabarti R, Vikramadithyan RK, Mullangi R et al. Antidiabetic and hypolipidemic activity of Helicteres isora in animal models. J Ethnopharmacol 2002; 81: 343-349
24 Schneider S, Ueberberg S, Korobeynikov A et al. Synthesis and evaluation of a Glibenclamide glucose-conjugate: A potential new lead compound for substituted Glibenclamide derivatives as islet imaging agents. Regul Pept 2007; 139: 122-127
25 Rathish IG, Javed K, Bano S et al. Synthesis and blood glucose lowering effect of novel pyridazinone substituted benzenesulfonylurea derivatives. Eur J Med Chem 2009; 44: 2673-2678
26 Meyer M, Chudziak F, Schwanstecher C et al. Structural requirements of sulphonylureas and analogues for interaction with sulphonylurea receptor subtypes. Br J Pharmacol 1999; 128: 27-34
27 Lawrence CL, Proks P, Rodrigo GC et al. Gliclazide produces high-affinity block of K ATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells. Diabetologia 2001; 44: 1019-1025
28 Yuriev E, Kong DC, Iskander MN. Investigation of structure-activity relationships in a series of Glibenclamide analogues. Eur J Med Chem 2004; 39: 835-847
29 Ahmed I, Lakhani MS, Gillett M et al. Hypotriglyceridemic and hypocholesterolemic effects of anti-diabetic Momordica charantia (karela) fruit extract in streptozotocin-induced diabetic rats. Diabetes Res Clin Pract 2001; 51: 155-161
30 Pari L, Venkateswaran S. Protective role of Phaseolus vulgaris on changes in the fatty acid composition in experimental diabetes. J Med Food 2004; 7: 204-209