Design and Synthesis of Hesperidin Derivatives With Anti-Inflammatory Potential.

Hesperidin is the primary active constituent of citrus fruits and exhibits a wide range of pharmacological activities. To identify more effective anti-inflammatory compound, 22 novel hesperidin derivatives incorporating fatty and cinnamic acid groups were designed and synthesized. Among them, compound B8 demonstrated the most potent inhibitory effect against LPS-induced NO production in RAW264.7 macrophages (IC50 = 10.4 ± 0.7 µM) with no significant cytotoxicity. Molecular docking with the NLRP3 protein demonstrated a favorable binding energy of -8.39 kcal/mol, while quantum chemical calculations provided insights into the interaction. These results provide a valuable structural design strategy for advancing the development of new hesperidin anti-inflammatory leads.