Synthesis and biological evaluation of unique stereodimers of sinomenine analogues as potential inhibitors of NO production

Inhibition of the excessive NO production has been recognized as a potential means for the treatment of rheumatoid arthritis (RA). In order to discover more potent inhibitors and explore the preliminary structure activity relationship, a series of unique stereodimers of sinomenine analogues were designed and synthesized. Their inhibitory activity on NO production and cytotoxicity were evaluated using LPS-activated murine macrophages RAW264.7 assay and MTT method, respectively. Among these compounds, 1a, 2, 2a, 2b, and 4 showed potent inhibitory activity on NO production without obvious cytotoxicity. Furthermore, 2, 2a, and 2b significantly suppressed mRNA expression of iNOS. Interestingly, (S)-dimers displayed a better bioactivity than (R)-dimers. These compounds may sever as lead candidates in the development of novel therapeutic drugs for RA treatment.

A series of unique stereodimers of sinomenine analogues were synthesized and evaluated on NO production and cytotoxicity. Dimer 2a and 2b showed the most potent inhibitory activity on NO production without obvious cytotoxicity and also significantly suppressed mRNA expression of iNOS. Interestingly, (S)-dimers displayed a better bioactivity than (R)-dimers.Figure optionsDownload as PowerPoint slide