State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China.
Phytochemistry. 2020 Apr;172:112260. doi: 10.1016/j.phytochem.2020.112260. Epub 2020 Jan 23.
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 IC values below 5.0 μM; nine compounds exhibited inhibition with IC values in the range of 7.8-28.4 μM. Furthermore, we demonstrated that preskimmianine suppressed the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor kappa B (NF-κB) in LPS-induced BV-2 microglial cells.
从秦皮中分离得到了 6 种未被描述的喹啉生物碱，分别命名为 dasycarines A-E，以及 18 种已知的生物碱。所有结构均基于 UV、IR、NMR 和 HRMS 光谱数据的综合分析进行阐明，并通过比较计算和实验 ECD 数据来确定绝对构型。(+)-Dasyrine A (1a) 和 (-)-Dasyrine A (1b) 是一对二聚呋喃喹啉生物碱的对映异构体，它们是通过呋喃的[2 + 2]环加成形成的第一个二聚体。(-)-Dasycarine A 的结构和绝对构型通过 X 射线晶体学确定。此外，所有分离得到的化合物均测试了其对 LPS 刺激的 BV-2 小胶质细胞中 NO 产生的抑制作用。三种化合物的 IC 值低于 5.0 μM，表现出强烈的抑制作用；九种化合物的 IC 值在 7.8-28.4 μM 范围内，表现出抑制作用。此外，我们证明了 preskimmianine 可以抑制 LPS 诱导的 BV-2 小胶质细胞中促炎细胞因子（如肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和核因子 kappa B（NF-κB）的水平。
