Microfluidics assisted synthesis and bioevaluation of sinomenine derivatives as antiinflammatory agents

Sinomenine (1) is currently used for the treatment of rheumatoid arthritis (RA) in China and there is still room for the improvement of its efficacy. In present study, capillary based microfluidic system was effectively applied for the syntheses of two novel series of sinomenine derivatives. The Heck reactions in microreactor gave much higher conversions compared to the batch ones. The two-step synthesis of the isoxazoline in microreactor greatly shortened the reaction time without any isolation of intermediates. The inhibitory activity of synthesized compounds on the TNF-α-induced nuclear factor kappa B (NF-κB) activation was evaluated in vitro. Among the compounds, 3c and 3g showed the potent inhibitory activity. Furthermore, 3g exhibited the antiinflammatory effect in vivo.

Graphical abstractNovel sinomenine derivatives were synthesized with the continuous flow capillary microreactor and their antiinflammatory activities were evaluated in vitro and in vivo.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Continuous flow capillary microreactor was effectively used. ► Two novel series of sinomenine derivative were synthesized with the microreactor. ► The antiinflammatory activities of synthesized compounds were evaluated in vitro and in vivo. ► 3g inhibited NF-κB activation and mouse paw edema.