240131-71-9Relevant academic research and scientific papers
Synthesis and biological evaluation of unique stereodimers of sinomenine analogues as potential inhibitors of NO production
Teng, Peng,Liu, Hai-Liang,Deng, Zhang-Shuang,Shi, Zhi-Bing,He, Yun-Mian,Feng, Li-Li,Xu, Qiang,Li, Jian-Xin
, p. 3096 - 3104 (2011)
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
Metabolic mechanism and anti-inflammation effects of sinomenine and its major metabolites N-demethylsinomenine and sinomenine-N-oxide
Kou, Fang,Li, Qiang,Lyu, Chunming,Wang, Yuyan,Wei, Hai,Zhou, Wenbin
, (2020/10/05)
Aims: Sinomenine (SIN) is clinically used as an anti-rheumatic drug. However, the metabolic and pharmacological mechanisms of SIN combined with its metabolites are unclear. This study aims to explore the cyclic metabolic mechanism of SIN, the anti-inflammation effects of SIN and its major metabolites (N-demethylsinomenine (DS) and sinomenine-N-oxide (SNO)), and the oxidation property of SNO. Materials and methods: SIN was administrated to rats via gavage. Qishe pills (a SIN-containing drug) were orally administrated to humans. The bio-samples were collected to identify SIN's metabolites. Enzymatic and non-enzymatic incubations were used to reveal SIN's metabolic mechanism. Impacts of SIN, SNO and DS on the inflammation-related cytokine's levels and nuclear translocation of NF-κB were evaluated in LPS-induced Raw264.7 cells. ROS induced by SNO (10 μM) was also assessed. Key findings: CYP3A4 and ROS predominantly mediated the formation of SNO, and CYP3A4 and CYP2C19 primarily mediated the formation of DS. Noteworthily, SNO underwent N-oxide reduction both enzymatically, by xanthine oxidase (XOD), and non-enzymatically, by ferrous ion and heme moiety. The levels of IL-6 and TNF-α and nuclear translocation of NF-κB were ameliorated after pretreatment of SIN in LPS-induced Raw264.7 cells, while limited attenuations were observed after pretreatment of DS (SNO) even at 200 μM. In contrast, SNO induced ROS production. Significance: This study elucidated that SIN underwent both enzymatic and non-enzymatic cyclic metabolism and worked as the predominant anti-inflammation compound, while SNO induced ROS production, suggesting more studies of SIN combined with SNO and DS are necessary in case of DDI and potential toxicities.
Access to a Structurally Complex Compound Collection via Ring Distortion of the Alkaloid Sinomenine
Garcia, Alfredo,Drown, Bryon S.,Hergenrother, Paul J.
, p. 4852 - 4855 (2016/10/18)
Many compound collections used in high-throughput screening are composed of members whose structural complexity is considerably lower than that of natural products. We previously reported a strategy for the synthesis of complex and diverse small molecules from natural products using ring-distortion reactions, called complexity-to-diversity (CtD), and herein, CtD is applied in the synthesis of 16 diverse scaffolds and 65 total compounds from the alkaloid natural product sinomenine. Chemoinformatic analysis shows that these compounds possess complex ring systems and marked three-dimensionality.
