Acetylcholinesterase inhibitors from Tetrapterys mucronata

Abstract

In our search for acetylcholinesterase (AChE) inhibitors, the investigation of Tetrapterys mucronata Cav. (Malpighiaceae), a plant used in Brazil for its psychotropic properties, was pursued. The methanolic extract of the bark of T. mucronata presented an interesting AChE inhibition in a TLC bioautographic assay. In order to isolate the active compounds, bioassay-guided isolation was undertaken using HPLC-microfractionation in 96 well plates and agar-overlay bioautography to localize the active compounds. The analytical HPLC-PAD conditions were geometrically transferred to a preparative medium pressure chromatography (MPLC-UV) by chromatographic calculations for the efficient isolation of the active compounds at the milligram scale in one step. Using this approach, 22 compounds were isolated, six of them being new natural products, such as 5-hydroxy-2-(2,3-dihydroxy-1-(1 H-indol-3-yl)propyl)-1 H-indole-3-carboxamide and 3-(2-(dimethylamino)ethyl)-2-(2,3-dihydroxy-1-(1 H-indol-3-yl)propyl)-1 H-indol-5-ol. The structure of the isolated compounds was elucidated by classical spectroscopic methods including UV, 2D NMR and HR-MS and chemical derivatisation. Some of the isolated compounds presented a strong AChE inhibition on the bioautographic assay; however those compounds showed weak activity when it was measured in solution.