(+)- 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

Abstract

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 (3–8) 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.