Design, synthesis and characterization of zinc-3 hydroxy flavone, a novel zinc metallo complex for the treatment of experimental diabetes in rats

Zinc is essential in the physiology of insulin and has prominent roles in the structural and functional aspects of insulin. Most of the zinc complexes so far tested for their antidiabetic potential exerts significant toxicity. Hence, the development of zinc complexes with various ligands in order to reduce the toxicity of zinc continues. In the present study, an attempt has been made to synthesize zinc-3-hydroxy flavone (Zn-flavonol) complex and it was subjected to spectral characterization. The UV-visible, IR, fluorescence, mass and NMR spectral studies provide information that complexation involves the binding of zinc ion with alpha hydroxyl keto group of the 3-hydroxy flavone (flavonol). Acute toxicity and dosage fixation studies revealed that the Zn-flavonol complex is non toxic and oral administration of the complex at a concentration of 5 mg/kg b.w./rat/day for 30 days to streptozotocin induced diabetic rats showed significant reduction in blood glucose, glycosylated hemoglobin (HbA1c), urea, uric acid and creatinine with concomitant improvement in plasma insulin and C-peptide levels. Further, the oral glucose tolerance test performed in experimental rats indicated that the Zn-flavonol complex has significant antihyperglycemic activity in streptozotocin induced diabetic rats. Also, the reduced activities of serum AST, ALT and ALP in the diabetic rats treated with the complex revealed the non-toxic nature of the zinc-flavonol complex. The antidiabetic activity of the complex was comparable with gliclazide, a standard antidiabetic drug. (C) 2012 Elsevier B. V. All rights reserved.