Studies On Synthesis Of α-Truxillicacid Derivativesand Inhibitory Effect On Nitric Oxide Production In RAW264.7Macrophages

Daphne aurantiaca Diels is a common evergreen shrub native to Yunnan and Sichuan provinces in China. Its stem bark is used for the treatment of injuries from falls and bruises in folk medicine. In our study, two interesting new innovanoside dimmers, diinnovanosides2and3, with an unusual four-member cyclobuatane ring, and isoinnovanoside (1), were isolated from the titled plant. However, it is rather difficult to confirm their configurations only by extensive spectral analysis.Therefore, we synthesized diinnovanoside2successfully and further confirmed absolute configuration of2. Compared with compound2, the relative configuration of3were obvious. Compounds1,2and3were evaluated in LPS-induced RAW264.7macrophages in vitro. The results showed compounds1,2and3were found to inhibit nitric oxide. In our study,4,4’-dihydroxy-α-truxillic acid was found to inhibit NO production, while its monomer component (E)-p-coumaric acid showed no activity. The result indicated that the dimeric structure played an important role in the expression of anti-NO activity. To the best of our knowledge, no existing literatures focus on the inhibitory effects of NO production by4,4’-dihydroxy-α-truxillic acid and its derivatives. structural diversity is important for the discovery of new NOS inhibitors, and structural complexity and diversity provide options for clinical research, which supports the theoretical basis for new clinical candidates with significant activity.To investigate the correlation between the structures of4,4’-dihydroxy-α-truxillic acid derivatives and inhibition of NO release and reports the discovery of a new lead compound for NOS inhibitors.4,4’-Dihydroxy-α-truxillic acid and its derivatives, MYT21-1a–MYT21-35a, were designed and synthesized and evaluated in LPS-induced RAW264.7macrophages in vitro. Cytotoxicity was also evaluated using a CCK-8assay. In particular, compound MYT21-10a showed significant inhibition on NO production with an IC50value of17.5μM, and no significant cytotoxicity was observed up to a concentration of50μM.