Synthesis of Some Vanillin Semicarbazones and Evaluation of their Anti diabetic and Associated Hypocholestremic Activities

Abstract

Superimposition of docking structures of compound 13 and 31 with PPARand#945;/and#947; revealed that these analogues superimposed well with each other, whereas the linker and the tail parts adopt different conformations. The 4-substituted aromatic centre allows the best fit to the binding site by providing the optimum distance between the acidic head and oxygen at C-4 position of aromatic centre, thus newlinemoving the hydrophobic tail on aromatic centre close to the hydrophobic region of protein consisting of serine, tyrosine and histidine, resulting in strong hydrophobic interactions with these residues. From these findings, it can be suggested that the designing of new chemical analogues of vanillin semicarbazones and its structural modification with a very interesting pharmacological profile lead the necessity of further research. A series of eight vanillin semicarbazones were synthesized from aniline/substituted aniline and their proposed structure was established by various analytical techniques such as IR, 1H NMR and MASS spectral studies. Log p value was found that all the newly synthesized vanillin semicarbazones have molecular and drug-likeness properties. Acute oral toxicity studies concluded that vanillin semicarbazones (I and II to IV) administered orally with 3g/kg and 5g/kg respectively did not show any toxic signs and mortality in mice. Anti-diabetic studies concluded that oral administration of vanillin semicarbazones (I-IV) significantly reduced high blood glucose level in streptozotocin (STZ) induced diabetes and attenuates total cholesterol and triglycerides in diabetic animals. This present study warrants the further exploration and exploitation of unified new vanillin semicarbazones for the management of hyperlipidemia associated Type II diabetes mellitus. Such a study provides precious information for drug development and also serving to highlight the areas for future research. Further characterization and advanced pharmacological studies on vanillin semicarbazones are under pipeline.