SYNTHESIS AND PRELIMINARY PHARMACOLOGICAL EVALUATION OF NEW NAPROXEN ANALOGUES HAVING 1, 2, 4-TRIAZOLE-3-THIOL

Monther F Mahdi,Noor H Naser,Nethal H Hammud

doi:10.22159/ijpps.2017v9i7.18273

Abstract

Objective: The objective of this search was to synthesize a new naproxen analogues having a 1,2,4-triazole-3-thiol heterocyclic ring, and preliminary pharmacological assessment of the anti-inflammatory activity of the synthesized compounds. Methods: The synthesis of naproxen analogues that having 1,2,4-triazole-3-thiol heterocyclic ring occur through esterification of naproxen, and then its reaction with hydrazine hydrate, and carbon disulfide, finally different aromatic aldehydes reacted with triazole derivatives of naproxen containing amino group to produce schiff bases.Results: In vivo acute anti-inflammatory activity of the synthesize compounds (Va-Vd) was evaluated in rats using egg-white induced edema model of inflammation in a dose equivalent to (50 mg/kg) of naproxen. All tested compounds were produced a significant reduction in paw edema with respect to the effect of propylene glycol 50% v/v (control group). Compound Vd produced superior anti-inflammatory activity compared to naproxen.Conclusion: The results obtained in this work give evidence about the valid synthesis of 1,2,4 triazole-3-thiol derivatives of naproxen, which reacted with different aldehydes to yield several schiff bases. The incorporation of benzaldehyde possess para-electron donating group (para-hydroxyl benzaldehyde) will increase the anti-inflammatory activity of naproxen.

Highlights

Non-steroidal anti-inflammatory drugs represent a group of the most widely used medications worldwide [1]
; the drugs that inhibit both these enzymes causes a wide range of side effects as bleeding, gastric ulceration and erosion, this will potentiate the direct effect of these medications as they are possess the carboxyl group which responsible for the gastric mucosal damage [9, 10]
While the selective agents were those inhibited the COX-2 only, e. g., celecoxib (III) and valdecoxib (IV), by that associated with fewer side effects as gastric ulceration and bleeding [14, 15]

Summary

Introduction

Non-steroidal anti-inflammatory drugs represent a group of the most widely used medications worldwide [1] They were used for the treatment of different inflammatory conditions as rheumatoid arthritis, and osteoarthritis, in addition to their analgesic and antipyretic properties [2, 3]. ; the drugs that inhibit both these enzymes causes a wide range of side effects as bleeding, gastric ulceration and erosion, this will potentiate the direct effect of these medications as they are possess the carboxyl group which responsible for the gastric mucosal damage [9, 10]. This group of non-steroidal called the nonselective drugs e. While the selective agents were those inhibited the COX-2 only, e. g., celecoxib (III) and valdecoxib (IV), by that associated with fewer side effects as gastric ulceration and bleeding [14, 15]

Methods

Results

Conclusion