Triterpenoids with Acetylcholinesterase Inhibition from Chuquiraga

A bioactivity-guided approach was taken to identify the acetylcholinesterase (AChE) inhibitory agents in the ethanolic extract of Chuquiraga erinacea D. Don. subsp. erinacea leaves using a bioautographic method. This permitted the isolation of the pentacyclic triterpenes calenduladiol (1), faradiol (2), heliantriol B2 (3), lupeol (4), and a mixture of alpha-and beta-amyrin (5a and 5b) as active constituents. Pseudotaraxasterol (6) and taraxasterol (7) were also isolated from this extract and showed no activity at the same analytical conditions. Compound 1 showed the highest AChE inhibitory activity with 31.2% of inhibition at 0.5 mM. Looking forward to improve the water solubility of the active compounds, the sodium sulfate ester of 1 was prepared by reaction with the (CH3)(3) N. SO3 complex. The semisynthetic derivative disodium calenduladiol disulfate (8) elicited higher AChE inhibition than 1 with 94.1% of inhibition at 0.5mM (IC50 = 0.190 +/- 0.003 mM). Compounds 1, 2, 3, 5, 6, and 7 are reported here for the first time in C. erinacea. This is the first report of AChE inhibition from calenduladiol (1) as well as from a sulfate derived from a natural product. Downloaded by: Thomson Reuters. Copyrighted material.