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 <b>2a</b>-<b>2e</b> 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 <b>2a</b>-<b>2e</b> had stable binding to the GBP5 protein. The compounds <b>2a</b>-<b>2e</b> showed stable binding to the GBP5 protein by molecular docking Pre-preparing the druggability of compounds <b>2a</b>-<b>2e</b> by ADEMT 3.0 showed that each derivative had similar druggability to sinomenine. The analgesic activity of compounds <b>2a</b>-<b>2e</b> 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 <b>2a</b>-<b>2e</b> had some analgesic effects. The results of the acetic acid writhing test showed that the analgesic effects of <b>2a</b>, <b>2c</b>, <b>2e</b> were better than that of sinomenine, and the other derivatives were equivalent to sinomenine. Compound <b>2b</b> showed excellent anti-inflammatory properties in mouse ear edema.