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 antinociceptive 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, 1 H NMR, 13 C 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 antiinflammatory activities. On the other hand, none of the tested compounds changed the reaction time of mice in hotplate 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.

Design, synthesis and pharmacological profile of (−)-verbenone hydrazones

“…In this study, bicyclic terpenoid (−)-verbenone was used as a base for hydrazone synthesis via its condensation with hydrazides of para-substituted phenoxyacetic acid. As known earlier, phenoxyacetic acid derivatives also possess the peripheral nociceptive action and anticonvulsant effect [12,13]. Taking into account the foregoing, a series of novel (−)-verbenone hydrazones were designed and synthesized, and their spectral characteristics have been described followed by their investigation as potential analgesic and anticonvulsant agents using different experimental models in vivo.…”

Mini Review on Therapeutic Profile of Phenoxy Acids and Thier Derivatives

“…Most of the derivatives were found to exhibit peripheral nociceptive effects. The results demonstrated that the presence of acidic moiety increased the peripheral antinociceptive activity and reduced the central antinociceptive activity [5]. 5) keeping in view that atropine induces central antinociception by increasing cholinergic transmission.…”

Design, Synthesis and Biological Evaluation of Novel N-Pyridyl-Hydrazone Derivatives as Potential Monoamine Oxidase (MAO) Inhibitors

“…The 2-[(2-substitutedbenzylidene)hydrazinyl]-6-ethoxy-3-nitropyridine derivatives 2a – 2n were synthesized by using a simple previously reported method [ 12 , 13 ] and in accordance with a protocol used in our earlier research. The structures of the synthesized compounds were completely identified by spectral data, as reported in the experimental section.…”