Amide–Iminoate Isomerism in Antineuroinflammatory Isoquinoline Alkaloids from <i>Stephania cepharantha</i>
Jiao Xiao, Junyu Song, Bin Lin, Wei Li, Yanqiu Yang, Jingyu Liu, Yue Hou, Gang Chen, Ning Li
Abstract
Six new (1–6) and two known (7, 8) alkaloids that were chemically inseparable geometrical isomers (two isomers present in a 1:1 ratio for 1–4 and 6 and a 1:3 ratio for 5, 7, and 8) were identified from Stephania cepharantha. Their structures and absolute configurations were determined by spectroscopic data analyses and comparison of their experimental and calculated ECD spectra. Moreover, using NOE correlations and DFT-based calculations, the NMR data of each geometrical isomer of 1–6 were assigned. The biological evaluation of 1–8 showed that 5 and 6 have stronger inhibitory effects (IC50 values, 12.0 and 12.6 μM, respectively) than minocycline (IC50 value, 17.5 μM) against NO production in overactivated BV2 cells, suggesting they have great potential in the development of neuroinflammatory therapeutics for treating neurodegenerative diseases.