Effect of a novel succinamic acid derivative as potential anti-diabetic agent in experimental diabetic rats

  • Nikhil Khurana Deptt. of Biochemistry, University College of Medical Sciences (Univ. of Delhi), Delhi, India
  • Pankaj Sharma Deptt. of Chemistry, University of Delhi, Delhi-110007, India
  • Sunita Bhagat Deptt. of Chemistry, Atma Ram Sanatan Dharma College (Univ. of Delhi), New Delhi, India
  • Suman Bala Sharma Deptt. of Biochemistry, University College of Medical Sciences (Univ. of Delhi), Delhi, India

Abstract

4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid which is a succinamic acid derivative has been synthesized in 3 step reaction with malic acid. Its structure confirmation was done by various techniques like 1H NMR, 13C NMR, & HRMS and is recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. In the present study, the effect of 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid on plasma glucose, serum insulin, serum lipid profile and lipid peroxidation in streptozotocin–nicotinamide induced type 2 diabetic model was investigated.  4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid was administered orally (20 mg/kg b.w.) to streptozotocin + nicotinamide (STZ + NAD) induced diabetic rats for 28 days. A significant increase in fasting blood glucose levels, HbA1c levels, Serum lipid profile (TG & TC) and in  the levels of Malonaldialdehyde (MDA, end product of lipid peroxidation) was observed in STZ +NAD diabetic rats whereas the levels of high density lipoprotein-cholesterol (HDL-C) and serum insulin levels were significantly decreased  in STZ + NAD induced diabetic rats The effect of 4-((benzyloxy)amino)-2-hydroxy-4-oxobutanoic acid was compared with glibenclamide, a reference drug. Treatment with 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid and glibenclamide resulted in a significant reduction of fasting blood glucose levels with increase in plasma insulin levels in diabetic treated rats. 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid also resulted in a significant improvement in serum lipids and lipid peroxidation products. Our results suggest the potential role of 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid in the management of type-2 diabetes mellitus experimental rats.


Keywords: 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid, dyslipidemia, streptozotocin induced diabetes, lipid peroxidation

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Author Biographies

Nikhil Khurana, Deptt. of Biochemistry, University College of Medical Sciences (Univ. of Delhi), Delhi, India

Deptt. of Biochemistry, University College of Medical Sciences (Univ. of Delhi), Delhi, India

Pankaj Sharma, Deptt. of Chemistry, University of Delhi, Delhi-110007, India

Deptt. of Chemistry, University of Delhi, Delhi-110007, India

Sunita Bhagat, Deptt. of Chemistry, Atma Ram Sanatan Dharma College (Univ. of Delhi), New Delhi, India

Deptt. of Chemistry, Atma Ram Sanatan Dharma College (Univ. of Delhi), New Delhi, India

Suman Bala Sharma, Deptt. of Biochemistry, University College of Medical Sciences (Univ. of Delhi), Delhi, India

Deptt. of Biochemistry, University College of Medical Sciences (Univ. of Delhi), Delhi, India

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Khurana N, Sharma P, Bhagat S, Sharma SB. Effect of a novel succinamic acid derivative as potential anti-diabetic agent in experimental diabetic rats. JDDT [Internet]. 15Dec.2018 [cited 27Jan.2021];8(6-s):57-2. Available from: http://jddtonline.info/index.php/jddt/article/view/2080