In Vivo Anti-Inflammatory Evaluation and In Silico Physicochemical Characterization of Flavanones from E. platycarpa Leaves

The inflammatory response is a defence mechanism triggered by tissue damage, aiming to eliminate harmful agents and initiate healing. Conventional anti-inflammatory drugs, such as NSAIDs and corticosteroids, are widely used but often cause severe side effects. Flavonoids, particularly flavanones, have shown significant anti-inflammatory activity with fewer adverse effects. In this study, eight analogues (<b>1a</b>-<b>1d</b>) and (<b>2a</b>-<b>2d</b>) were obtained from natural flavanones (<b>1</b>) and (<b>2</b>) using a pharmacomodulation strategy. NMR, FTIR, structurally confirmed all compounds and MS. Theoretical physicochemical analyses, including molecular orbital energies, dipole moments, and Log P, suggested favourable drug-like properties for these analogues. The anti-inflammatory activity was evaluated in vivo using a TPA-induced mouse ear edema model. Analogue (<b>2c</b>) exhibited the highest inhibition (98.62 ± 1.92%), followed by (<b>2d</b>) (76.12 ± 1.74%) and (<b>1c</b>) (71.64 ± 1.86%). Notably, structural modifications such as cyclization, methoxylation, and prenylation were associated with increased lipophilicity and biological activity, suggesting that tuning physicochemical properties may enhance pharmacological efficacy while preserving drug-likeness. Overall, these findings highlight semi-synthetic derivatization of flavanones as a valuable approach for developing potent and selective anti-inflammatory agents, positioning analogue (<b>2c</b>) as a promising lead for further pharmacological development.