pH-dependent, stereoselective dimerization of sinomenine.
In a continuing study on discovery of more potent derivatives of sinomenine (1), a clinically available alkaloid for rheumatoid arthritis (RA) treatment, oxidation of sinomenine provided two unique stereoisomers, disinomenines 2 and 3. The structure of 3 was determined by MS, NMR, and X-ray analysis. The formation of 2 and 3 via oxidation of sinomenine by potassium permanganate (KMnO4) exhibited a pH-dependent stereoselectivity. The bioassay results using human synovial sarcoma cells (SW982) showed that 2 inhibited, while 3 stimulated, IL-6 production.
Deng
Zhang-Shuang
ZS
Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, PR China.
Zhao
Yu
Y
He
Cui-Cui
CC
Jin
Jie
J
He
Yun-Mian
YM
Li
Jian-Xin
JX
D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015850:Interleukin-6 / Q000096:biosynthesis; D009019:Morphinans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D013584:Sarcoma, Synovial / Q000378:metabolism; D013237:Stereoisomerism; D000093242:Interleukin-6 Inhibitors
D015850:Interleukin-6; D009019:Morphinans; D000093242:Interleukin-6 Inhibitors; C009271:sinomenine