Synthesis and anti-nociceptive, anti-inflammatory activities of new aroyl propionic acid derivatives including N-acylhydrazone motif

Abstract

In the present study, new 4-[4-[2-(2-(4-substituted benzylidene)hydrazinyl)-2-oxoethoxy]phenyl]-4-oxobutanoic acid derivatives were synthesized, and their anti-nociceptive and anti-inflammatory activities were investigated. In the synthesis of the compounds, 4-[4-(2-ethoxy-2-oxoethoxy)phenyl]-4-oxobutanoic acid molecule was used as starting material. The intermediate hydrazide compound (1) was reacted with appropriate aromatic aldehydes to obtain final hydrazone compounds (2a–i). All final compounds are well characterized by IR, 1H NMR, 13C NMR, and MS spectroscopic data. Hot-plate and tail-clip tests, measuring centrally organized responses to a nociceptive stimulus, were performed in order to examine anti-nociceptive potentials of the compounds (50 mg/kg). In addition, peripherally mediated anti-nociceptive effect was assessed by acetic acid-induced writhing tests. Further, carrageenan-induced paw edema method was used in order to evaluate the anti-inflammatory activity potential of the compounds. Motor coordination of the animals was examined in a Rota-rod apparatus. The obtained data indicated that compounds 2a, 2b, 2c, 2d, 2e, 2f decreased the number of acetic acid-induced writhing behaviors comparable with diclofenac sodium (10 mg/kg). The same compounds significantly decreased the paw swelling rate (%) of the mice with respect to the control values. These results indicated that compounds 2a, 2b, 2c, 2d, 2e, and 2f have peripherally mediated anti-nociceptive and anti-inflammatory activities. On the other hand, none of the tested compounds changed the reaction time of mice in hot-plate or tail-clip tests indicating that neither supraspinal nor spinal pathways were affected. The observed effect seems to be specific, since Rota-rod tests did not point out any motor impairment induced by the test compounds.