Novel Flurbiprofen Derivatives as Antioxidant and Anti-Inflammatory Agents: Synthesis, In Silico, and In Vitro Biological Evaluation

Abstract

In this study, we present the synthesis of five novel compounds by combining flurbiprofen with various substituted 2-phenethylamines. The synthesized derivatives underwent comprehensive characterization using techniques such as 1H- and 13C-NMR spectroscopy, UV-Vis spectroscopy, and high-resolution mass spectrometry (HRMS). Detailed HRMS analysis was performed for each of these newly created molecules. The biological activities of these compounds were assessed through in vitro experiments to evaluate their potential as anti-inflammatory and antioxidant agents. Furthermore, the lipophilicity of these derivatives was determined, both theoretically using the cLogP method and experimentally through partition coefficient (RM) measurements. To gain insights into their binding affinity, we conducted an in silico analysis of the compounds’ interactions with human serum albumin (HSA) using molecular docking studies. Our findings reveal that all of the newly synthesized compounds exhibit significant anti-inflammatory and antioxidant activities, with results statistically comparable to the reference compounds. Molecular docking studies further explain the observed in vitro results, shedding light on the molecular mechanisms behind their biological activities. Using in silico method, toxicity was calculated, resulting in LD50 values. Depending on the administration route, the novel flurbiprofen derivatives show lower toxicity compared to the standard flurbiprofen.

Synthesis of Flurbiprofen Based Amide Derivatives as Potential Leads for Diabetic Management: In Vitro α‐glucosidase Inhibition, Molecular Docking and DFT Simulation Approach

“…[32] Medicinal chemists have reported the synthesis and biological activities of flurbiprofen derivatives including, Manolov et al, reported the synthesis, anti-oxidant and anti-inflammatory activities of novel amide derivatives with outstanding results. [33] Likewise, Momin et al, reported the synthesis with α-amylase inhibitory activity of flurbiprofen based oxadiazoles, [19] while Sajjad with his team members reported the synthesis and urease inhibition activity of novel derivatives with excellent results. [18,34] Inaddition, our group have reported the synthesis, α-glucosidase inhibition, [21] analgesic and anti-inflammatory activities [35] of novel derivatives of the drug flurbiprofen.…”