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.
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