New Biguanides as Anti-Diabetic Agents Part I: Synthesis and Evaluation of 1-Substituted Biguanide Derivatives as Anti-Diabetic Agents of Type II Diabetes Insulin Resistant

Abstract

New 1-substituted-biguanide hydrochloride salts were synthesized via reacting benzo[1,3-d]dioxol-5-amine, phenylhydrazine, N,N-dimethylhydrazinecarboxamide, benzohydrazide and 2-phenyl acetohydrazide with dicyandiamide in acidic medium. Structures of the obtained biguanide salts were characterized by spectroscopic tools. The synthesized compounds were screened for their anti-diabetic activity with standard metformin drug. Oral treatment of hyperglycemic rats with the synthesized biguanide derivatives significantly decreased the elevated blood glucose level. Additionally, anti-diabetic properties towards liver function enzyme activities (AST, ALT and ALP), lipids profiles (TC, TG and TL), lipid peroxide and nitrous oxide as well as histopathological studies relative to metformin hydrochloride were investigated and discussed.

Key words

diabetes mellitus - biguanides - metformin - anti-diabetic drug

• References

• 1 Skyler JS. Diabetes mellitus: pathogenesis and treatment strategies. J Med Chem 2004; 47: 4113-4117
• 2 Hundal RS, Inzucchi SE. Metformin: new understandings, new uses. Drugs 2003; 63: 1879-1894
• 3 Huttunen KM, Mannila A, Laine K. et al. The first bioreversible prodrug of metformin with improved lipophilicity and enhanced intestinal absorption. J Med Chem 2009; 52: 4142-4148
• 4 Selvi M. Insulin and hypoglycemic agents. burger’s medicinal chemistry and drug discovery”. 6th ed. Ed. Abraham DJ. New York: A Wiley-Interscience Publication, John Wiley & Sons, Inc; 2003: 1
• 5 Emerick AJ, Richards MP, Kartje GL. et al. experimental diabetes attenuates cerebral cortical−evoked forelimb motor responses. Diabetes 2005; 54: 2764-2771
• 6 Milani E, Nikfar S, Khorasani R. et al. Reduction of diabetes-induced oxidative stress by phosphodiesterase inhibitors in rats. Comparative biochemistry and physiology part C. Toxicology and Pharmacology 2005; 140: 251-255
• 7 Salama RM, Schaalan MF, Ibrahim ME. et al. Effectiveness of telmisartan as an adjunct to metformin in treating type ii diabetes mellitus in rats. Open Journal of Endocrine and Metabolic Diseases 2013; 3: 186-196
• 8 Sharma SS, Ramani JV, Dalwadi DP. et al. New ternary transition metal complexes of 2-{[(2-aminophenyl)imino] methyl}-phenol and metformin: synthesis, characterization and antimicrobial activity. E-Journal of Chemistry 2011; 8: 361-367
• 9 LeBel O, Maris T, Duval H. et al. A practical guide to arylbiguanides: synthesis and structural characterization. Can J Chem 2005; 83: 615-625
• 10 Abbas SY, Basyouni WM, El-Bayouki KAM. et al. Synthesis and evaluation of 1-substituted-biguanide derivatives as anti-diabetic agents for type ii diabetes insulin resistant. drug res/arzneimittelforschung 2016; 66: 377-383