Synthesis and anti-inflammatory activity evaluation of pterostilbene-based phthalide derivatives.

In recent years, phthalide and pterostilbene have been widely studied as important natural products. In this project, we designed and synthesized two series (a total of 37) of pterostilbene-phthalide heterozygous derivatives. The activities of all synthesized compounds were evaluated by LPS-induced RAW264.7 macrophages. The results demonstrated that all phthalide-phthalimide hybrids effectively inhibited NO release, with F22 showing the most significant inhibitory effect. Moreover, MTT assays confirmed that none of the compounds showed significant cytotoxicity. Mechanistic studies revealed that F22 significantly inhibited inducible iNOS and COX-2 expression and effectively suppressed the phosphorylation of IκB and p65 proteins in the NF-κB signaling pathway as well as phosphorylation of p-JNK, p-p38, and p-ERK in the MAPK pathway. These findings indicate that the anti-inflammatory activity of F22 is mediated through inhibition of the NF-κB/MAPK signaling pathways. In vivo studies demonstrated that F22 effectively alleviated dextran sulfate sodium salt-induced acute colitis in mice. In summary, F22 exhibits promising potential as an anti-inflammatory agent and holds significant value for the development of novel anti-inflammatory drugs.