In vivo anti-inflammatory evaluation of oxadiazole derivatives bearing flurbiprofen moiety using experimental and computational approaches

Abstract

Abstract Improving anti-inflammatory and analgesic drugs with negligible adverse effects remains a significant challenge for long-term use. In the present study, flurbiprofen-based oxadiazole derivatives were synthesized and evaluated for their in vivo anti-inflammatory activity using the carrageenan-induced paw edema assay in mice. Amongst the tested compounds, 10, 3, and 5 exhibited remarkable anti-inflammatory activity, with edema inhibition rates of 88.33%, 66.66%, and 55.55% respectively, compared to the standard drug flurbiprofen, which showed a 90.01% reduction. Molecular docking studies confirmed stable interactions of these compounds with the COX-2 binding site, similar to those observed with the standard drug flurbiprofen. Moreover, toxicity predictions, ADME profiles, and bioactivity scores were evaluated, along with frontier molecular orbitals (HOMO and LUMO) and the molecular electrostatic potential maps (MEP), to reveal the compounds’ drug-like properties and chemically reactive regions. These findings highlight the potential of these derivatives as promising candidates for further development as anti-inflammatory agents.

Keywords

• Flurbiprofen
• Oxadiazole
• In vivo anti-inflammatory
• Molecular docking
• DFT and molecular dynamic simulation