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 x 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 (ACNE) and human plasma butyrylcholinesterase (BChE) were further studied, and their IC50 values for human RBC ACNE were 6.4 +/- 0.003 mu M,16.9 +/- 0.018 mu M, 5.7 +/- 0.004 mu M, 6.5 +/- 0.013 mu M and 7.7 +/- 0.001 mu M, respectively, and the IC50 values for human plasma BChE were 12.5 +/- 0.026 mu M, 2.1 +/- 0.005 mu M, 5.2 +/- 0.002 mu M, 7.3 +/- 0.005 mu M and 0.7 +/- 0.001 mu M, respectively. These data suggest, therefore, that N-demethylpuqietinone, hupeheninoside, ebeiedinone, yibeinoside A and chuan-beinone have both anti-RBC ACNE and anti-plasma BChE activities, N-demethylpuqietinone is a selective inhibitor of ACNE, whereas hupeheninoside and chuanbeinone are the selective inhibitors of BChE.