Flavanone Analogue 2c (Universidad Autónoma del Estado de Morelos)

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 (1a–1d) and (2a–2d) were obtained from natural flavanones (1) and (2) 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 (2c) exhibited the highest inhibition (98.62 ± 1.92%), followed by (2d) (76.12 ± 1.74%) and (1c) (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 (2c) as a promising lead for further pharmacological development.