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.
State Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
Jie
J
Jin
Peng
P
Teng
Hai-Liang
HL
Liu
Jing
J
Wu
Yu-Mei
YM
Liu
Qiang
Q
Xu
Jian-Xin
JX
Li
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D008813:Mice, Inbred ICR; D046210:Microfluidic Analytical Techniques; D008958:Models, Molecular; D009019:Morphinans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D041681:NIH 3T3 Cells; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009019:Morphinans; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C009271:sinomenine; D002351:Carrageenan