title: Synthesis and biological evaluation of unique stereodimers of sinomenine analogues as potential inhibitors of NO production.
abstract: 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.
authors.affiliation: Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Teng
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Liu
authors.forename: Zhang-Shuang
authors.initials: ZS
authors.lastname: Deng
authors.forename: Zhi-Bing
authors.initials: ZB
authors.lastname: Shi
authors.forename: Yun-Mian
authors.initials: YM
authors.lastname: He
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Feng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Li
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019281:Dimerization; D015870:Gene Expression / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D013237:Stereoisomerism
chemical_list: D009019:Morphinans; D012333:RNA, Messenger; D009569:Nitric Oxide; C009271:sinomenine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse