Abstract

SYNTHESIS, CHARACTERIZATION AND ANTI-DIABETIC ACTIVITY OF VANILLIN BASED ACETOHYDRAZIDE-HYDRAZONE DERIVATIVES

M. Upendar Reddy* and M. C. Somasekhara Reddy

Abstract

Hydrazide–hydrazone derivatives are present in many bioactive molecules and display a wide variety of biological activities, such as antibacterial, antitubercular, antifungal, anticancer, anti-inflammatory, anticonvulsant, antiviral and antiprotozoal action. The present paper describes the synthesis, characterization and anti-diabetic activity studies of vanillin based acetohydrazide-hydrazone derivatives. The synthesis involves the utilization of 2-phenylacetic acids and vanillin as starting materials. The direct conversion of 2-phenylacetic acids to 2-phenylacetohydrazides was accomplished in presence of HATU as peptide reagent, resulting in 88-92% yield. Coupling of vanillin 1 with 4-(bromomethyl)benzonitrile in 2-methyl-tetrahydrofuran in presence of potassium carbonate gave 4-((4-formyl-2-methoxyphenoxy)methyl)benzonitrile in 94% yield. Coupling of 4-((4- formyl-2-methoxyphenoxy)methyl)benzonitrile with 2-phenylacetohydrazides in ethanol at 75oC resulted in the formation of corresponding substituted phenyl-acetic acid [4-(4-cyanobenzyloxy)- 3-methoxy-benzylidene]-hydrazides in 88-90% yield. The structures of these derivatives were determined by 1H NMR, IR, mass spectroscopic techniques. These compounds were evaluated for their in vivo for their oral hypoglycemic activity by alloxan induced diabetic model in rat (anti-diabetic studies). Among all the derivatives, compound with substitution R = 2,3-dihydrobenzofuran was found to exhibit significant hypoglycemic activity (65.35%) when compared to insulin as a reference drug which showed 69.77% blood glucose lowering activity.

Keywords: Acetohydrazide, Anti-diabetic, Hydrazone, Synthesis, Vanillin.