Identification of Acetylcholinesterase Inhibiting Natural Products From Buxus natalensis and Drypetes gossweileri.

Abstract

This thesis describes phytochemical studies on two medically important plants, Buxus natalensis and Drypetes gossweileri. Chemical investigation on the acetylcholinesterase inhibiting chloroform extracts, obtained at pH 7.0 and 9.5 resulted in the isolation of seven natural products: O10-natafuranamine (123), cyclonataminol A (124), 31-demethylbuxaminol A (125), buxaminol A (126), buxaminol C (127), p coumaroylputrescine (128) and methyl syringate (129). Compound 123 is a member of a rarely occurring class of Buxus alkaloids containing a tetrahydrofuran ring incorporated in its structure. Compounds 123-129 were isolated for the first time from this plant. Structures of compounds 123-129 were elucidated with the aid of NMR and MS spectral data. All of these isolates exhibited different levels of AChE inhibitory activities with compound 123 being significantly active in this bioassay with an IC50 of 8.5 µM compared to the rest of the isolates. Compounds 123-129 were inactive in antimicrobial assays. Phytochemical studies on the crude extract of Drypetes gossweileri resulted in the isolation of a new N-linked aromatic glycoside, N-β-glucopyranosyl-p-hydroxy phenyl acetamide (151), along with two known compounds, p-hydroxy phenyl acetic acid (152) and p hydroxyphenyl acetonitrile (153). Compounds 151-153 exhibited moderate to weak AChE inhibitory activities.