Antidepressant Activity Of 1,3,4-Oxadiazole Scaffolds Incorporated Piperine Derivatives

Abstract

In the present study, ten derivatives of Piperine were synthesized by incorporating 1, 3, 4-oxadiazole scaffolds via a four steps reaction synthetic scheme. First step involves synthesis of (2E,4E)-5-(1,3-benzodioxol-5-yl)penta-2,4-dienoic acid(1) from isolated Piperine in ethanol. In the second step an ester methyl (2E,4E)-5-(1,3-benzodioxol-5-yl)penta-2,4-dienoate(2), has been synthesized by esterification of (1) with ethyl alcohol and concentrated H2SO4. This is then converted into (2E,4E)-5-(1,3-benzodioxol-5-yl)penta-2,4-dienehydrazide(3) in third step by hydrogenolysis in the presence of hydrazine hydrate. In the fourth step, Piperine derivatives (4a-4j) were synthesized by treating the hydrazide (3) with various p-substituted aromatic acids such as benzoic acid/p-hydroxy benzoic acid/ p-nitro benzoic acid/ p-amino benzoic acid/ p-bromo benzoic acid/ p-chloro benzoic acid/ p-fluoro benzoic acid/ p-methyl benzoic acid/ p-methoxy benzoic acid/ p-ethoxy benzoic acid in ethanol and phosphorous oxychloride. The synthesized compounds were confirmed by melting point, TLC, IR and 1H NMR studies and are in good agreement with assigned structures. Antidepressant activity of 4a, 4b and 4c was carried out using forced swimming test model. Among three derivatives tested 4a and 4b were found to possess profound antidepressant activity.