Semi-Synthesis and Biological Evaluation of Novel Sinomenine Derivatives

Sinomenine has long been known as an anti-inflammatory drug, while poor efficiency and large-dose treatment had limited its further application. Five novel sinomenine 1-Br-4-cinnamic acid esters derivatives 2a-2e were designed and synthesized to improve its analgesic and anti-inflammatory activity. All synthesized sinomenine derivatives were structurally confirmed by NMR and ESI-MS. Molecular docking results showed that compounds 2a-2e had stable binding to the GBP5 protein. The compounds 2a-2e showed stable binding to the GBP5 protein by molecular docking Pre-preparing the druggability of compounds 2a-2e by ADEMT 3.0 showed that each derivative had similar druggability to sinomenine. The analgesic activity of compounds 2a-2e was preliminarily determined by hot plate and acetic acid writhing experiments, while anti-neuroinflammatory effects were evaluated by a xylene-induced mouse ear edema model. The results of the hot plate method showed that the synthesized sinomenine derivatives 2a-2e had some analgesic effects. The results of the acetic acid writhing test showed that the analgesic effects of 2a, 2c, 2e were better than that of sinomenine, and the other derivatives were equivalent to sinomenine. Compound 2b showed excellent anti-inflammatory properties in mouse ear edema.