Hybrids of aurantiamide acetate and isopropylated genipin as potential anti‐inflammatory agents: The design, synthesis, and biological evaluation

A novel series of hybrids designed on the basis of aurantiamide acetate and isopropylated genipin were synthesized and biologically evaluated as anti‐inflammatory agents. Among them, compound 7o exhibited the best inhibitory activity against TNF‐α secretion (IC50 = 16.90 μM) and was selected for further in vitro and in vivo functional study. The results demonstrated that 7o was capable of suppressing the expression of LPS‐induced iNOS and COX‐2, as well as reducing the production of NO at the concentration of 5 μM, which may be resulted from its regulation of NF‐κB signaling and MAPK signaling. Moreover, compound 7o exhibited favorable in vivo anti‐inflammatory activity with an inhibition rate of 53.32% against xylene‐induced ear swelling in mice at the dose of 5 mg/kg. A series of novel anti‐inflammatory hybrids designed and synthesized based on aurantiamide acetate and isopropylated genipin. Among them, compound 7o exhibited the best inhibitory activity against TNF‐α secretion (IC50 = 16.90 μM). And it can regulate NF‐κB signaling and MAPK signaling. Moreover, compound 7o exhibited favorable anti‐inflammatory activity against xylene‐induced ear swelling in mice.