Inhibitors of Acetylcholine Esterase in vitro - Screening of Steroidal Alkaloids from Fritillaria Species

18 alkaloids were successfully isolated from five Fritillaria species and 5 derivatives were synthesized. Their effects on the bioactivity of human whole blood cholinesterase (ChE) were assessed. The results showed that N-demethylpuqietinone, hupeheninoside, ebeiedinone, yibeinoside A and chuanbeinone inhibited the bioactivity of human whole blood ChE at the concentration of 1.0 × 10 - 4 M, with the inhibitory effects of 55.5 ± 2.7 %, 66.8 ± 2.0 %, 69.0 ± 1.7 %, 71.2 ± 1.8 % and 70.7 ± 3.3 %, respectively. The effects of the five alkaloids on human red blood cell (RBC) acetylcholinesterase (AChE) and human plasma butyrylcholinesterase (BChE) were further studied, and their IC50 values for human RBC AChE were 6.4 ± 0.003 μM, 16.9 ± 0.018 μM, 5.7 ± 0.004 μM, 6.5 ± 0.013 μM and 7.7 ± 0.001 μM, respectively, and the IC50 values for human plasma BChE were 12.5 ± 0.026 μM, 2.1 ± 0.005 μM, 5.2 ± 0.002 μM, 7.3 ± 0.005 μM and 0.7 ± 0.001 μM, respectively. These data suggest, therefore, that N-demethylpuqietinone, hupeheninoside, ebeiedinone, yibeinoside A and chuanbeinone have both anti-RBC AChE and anti-plasma BChE activities, N-demethylpuqietinone is a selective inhibitor of AChE, whereas hupeheninoside and chuanbeinone are the selective inhibitors of BChE.