Synthesis, Anti-Inflammatory Evaluation, Antioxidant Activityand Molecular Docking Of New Hydrazide-Hydrazones Derived From Tolfenamic Acid

Abstract

Presented work included synthesis of tolfenamic ethyl ester from reaction of tolfenamic acid with ethanol absolute to form ethyl tolfenamate(1), which converted into tolfenamic acid hydrazide(2) by hydrazine hydrate.A novel series of hydrazide-hydrazones4(a-i) have been synthesized by reaction of tolfenamic acid hydrazide(2) with substituentsbenzaldehyde3(a-i). The newly synthesized compounds were elucidated by available spectral techniques: FT-IR, ¹H NMR, and ¹³C NMR. All synthesized compounds were screened in vivo as anti-inflammatory agents by the carrageenan induced paw edema model. The compounds 1 and 2 showed high anti-inflammatory activity, while the compounds 4a and 4g showed good anti-inflammatory activity. The antioxidant activity of all these compounds was performed in vitro by scavenging activity on 2,2-diphenyl-1-bicrylhydrazyl (DPPH), where the (1, 2, 4e and 4i) derivatives showed good antioxidant activity compared with ascorbic acid as a reference. The docking studies were performed for the compounds that exhibited anti-inflammation potency by using Auto Dock 4.2.6 programs to predict the binding modes of these compounds with the binding pocket of the COX-2 enzyme (PDB:ID:5ikt) in order to interpret their anti-inflammatory activity.