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(+)- and (-)-Corydecumbenines A and B, two pairs of novel quaternary protoberberine alkaloid cycloadduct enantiomers with anti-neuroinflammatory and neuroprotective activities from the rhizomes of Corydalis decumbens.
Bioorganic Chemistry ( IF 4.5 ) Pub Date : 2020-09-02 , DOI: 10.1016/j.bioorg.2020.104251
Xu Yin 1 , Hongli Jia 1 , Qingying Zhang 1 , Yong Jiang 1 , Pengfei Tu 1
Affiliation  

Two novel Diels-Alder [4 + 2] cycloadducts of quaternary protoberberine alkaloids and fumaric acid monoanion, corydecumbenines A and B (1 and 2), and six known isoquinoline analogues (38) were isolated from the rhizomes of Corydalis decumbens. The planar structures of 1 and 2 were elucidated by extensive spectroscopic analysis including UV, IR, HRESIMS, 1D and 2D NMR. Chiral chromatography of 1 and 2 afforded two pairs of enantiomers (+)-corydecumbenine A (1a), (–)-corydecumbenine A (1b), (+)-corydecumbenine B (2a), and (–)-corydecumbenine B (2b), respectively, and their absolute configurations were determined by single-crystal X-ray crystallography and comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1b and 2b exhibited significant nitric oxide (NO) inhibitory activities in lipopolysaccharide (LPS)-stimulated BV-2 cells with IC50 values of 11.6 and 16.2 μM, respectively, comparable to the positive control indomethacin (IC50 = 10.3 μM), and they could also decrease the level of interleukin (IL)-1β in BV-2 cells in a dose-dependent manner. Most of the isolates showed neuroprotective effects against the injury of OGD/R-induced PC12 cells at 20 μM.



中文翻译:

(+)-和(-)-大黄素A和B,两对新的季原小ber碱生物碱环加合物对映体,具有延胡索根茎的抗神经炎和神经保护活性。

两种新型狄尔斯-阿尔德[4 + 2]季生物碱小檗碱和富马酸单阴离子的cycloadducts,corydecumbenines A和B(12),和六个已知异喹啉类似物(3 - 8)购自根茎分离延胡索斜卧。通过广泛的光谱分析(包括UV,IR,HRESIMS,1D和2D NMR)阐明了12的平面结构。12的手性色谱分离得到两对对映异构体(+)-双十二烷基苯丙氨酸A(1a),(-)-十二烷基苯丙氨酸A(1b),(+)-十二烷基苯丙氨酸B(2a)和(-)-二十二烷基苯丙氨酸B(2b),它们的绝对构型是通过单晶X射线晶体学以及实验和计算的电子圆二色性(ECD)光谱进行比较确定的。化合物1b2b在脂多糖(LPS)刺激的B​​V-2细胞中表现出明显的一氧化氮(NO)抑制活性,其IC 50值分别为11.6和16.2μM,与阳性对照消炎痛(IC 50  = 10.3μM)相当,并且它们还能够降低白细胞介素的电平(IL)-1 β在BV-2细胞中呈剂量依赖性。大多数分离株在20μM时对OGD / R诱导的PC12细胞的损伤均表现出神经保护作用。

更新日期:2020-09-10
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