Synthesis, Biological Evaluation and Docking Studies of N-(2-benzamido feruloyl) Aryl Hydrazone Analogues

Background: Nowadays inflammation recognized as the underlying basis of number of diseases but still NSAIDS are the first drugs of choice having several side effects. In addition to that, oxidative stress also triggers the inflammation. This creates an initiation to introduce new molecules which act as efficient COX-2 inhibitors with diminished side effects. Objective: As a part of our search for newer agents, we designed a series of N-acylhydrazones by combining the pharmacophoric features of hydrazones with feruloyl derivatives in hope of enhancing the activity profile of title compounds. Methods: The title compounds (3a-l) were synthesized by the condensation of α-benzamido-(4- hydroxy-3-methoxy)-cinnamhydrazide (2) with different aromatic aldehydes in acidic conditions and characterized by elemental, spectral (IR, 1H NMR, 13C NMR, MASS) data and also evaluated for antiinflammatory (in-vivo, in-vitro and docking), analgesic and antioxidant activities. Results: The in-vivo anti-inflammatory data revealed that compounds 3j and 3i reduced the edema by 74% and 72% respectively at 100 mg /kg which is comparable to the standard, supported by in-vitro studies (3j: 10μM and 3i: 16μM as IC50) and also showed good docking scores (3j:-10.28 and 3i:- 10.13). The analgesic activity profile suggested that compounds 3j (65%) and 3e (60%) exhibited good activity by writhing test. Besides having good anti-inflammatory activity, title compounds also exhibited appreciable antioxidant potential evaluated by four in-vitro methods. Compounds 3j and 3f displayed good antioxidant potential than the standard by lipid peroxidation and DPPH scavenging methods respectively. Conclusion: Results suggested that the compound 3j emerged as a lead compound having multi target affinities.