Anti-inflammatory quinoline alkaloids from the root bark of Dictamnus dasycarpus

Six undescribed quinoline alkaloids, named dasycarines A-E, and 18 known ones were isolated from the root bark of Dictamnus dasycarpus. All the structures were elucidated on the basis of comprehensive analysis of UV, IR, NMR, and HRMS spectroscopic data, and the absolute configurations were assigned via comparison of the calculated and experimental ECD data. (+)-Dasycarine A (1a) and (-)-Dasycarine A (1b) are a pair of enantiomers of dimeric furoquinoline alkaloid, which are the first dimeric via [2 + 2] cycloaddition of furan. The structure and absolute configuration of ( - )-dasycarine A was determined via X-ray crystallography. Additionally, all the isolated compounds were tested for their inhibitory effects on NO production stimulated by LPS in BV-2 microglial cells. Three compounds showed strong inhibition with IC50 values below 5.0 mu M; nine compounds exhibited inhibition with IC50 values in the range of 7.8-28.4 mu M. Furthermore, we demonstrated that preskimmianine suppressed the levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nuclear factor kappa B (NF-kappa B) in LPS-induced BV-2 microglial cells.