No abstract

The pharmacotherapy for Alzheimer's disease (AD) includes the use of acetylcholinesterase inhibitors (AChEI). Recent investigations for novel AD therapeutic agents from plants suggested that Tabernaemontana genus is a promising source of novel anticholinesterasic indole alkaloids. In this work two fast screening techniques were combined in order to easily identify novel cholinesterase inhibitors (ChEI). Gas chromatography-mass spectrometry (GC-MS) of the less polar alkaloidic fractions obtained from the acid-base extraction of the stalk of T. laeta revealed thirteen monoindole alkaloids, four of them confirmed by co-injection with previously isolated alkaloids. The others were tentatively identified by mass fragmentation analysis. By gas chromatography with flame ionization detection (GC-FID) and using isatin as internal standard, affinisine and voachalotine were determined as major compounds. These fractions and fourteen previously isolated alkaloids, obtained from root bark of T. laeta and T. hystrix were investigated for acetyl (AChE) and butyrylcholinesterase (BuChE) inhibitory activities by the modified Ellman's method in thin layer chromatography (TLC-ChEI). Results showed selective inhibition of the alkaloids heyneanine and N b -methylvoachalotine for BuChE, and 19-epi-isovoacristine for AChE, whereas olivacine, affinisine, ibogamine, affinine, conodurine and hystrixnine inhibited both enzymes. In addition to confirming that monoterpenoid indole alkaloids can be novel therapeutic agents for AD, this is the first report of the ChEI activity of olivacine, a pyridocarbazole alkaloid.

Um novo alcalóide quaternário natural, N b -metilvoachalotina (1), três alcalóides indólicos diméricos, conodurina (2), voacamina (3) e tabernamina (4), e os três alcalóides monoméricos 19S-heyneanina (5), coronaridina (6) e voacangina (7) foram isolados da casca das raízes de Tabernaemontana laeta. Os triterpenos conhecidos 3-O-acetil-a-amirina, 3-O-acetil-b-amirina, 3-O-acetil-lupeol e 3-O-acetiltaraxasterol e os fitoesteróides b-sitosterol e seu derivado 3-O-b-Dglicopiranosídeo foram também identificados. As estruturas dos compostos foram elucidadas com base na análise de dados espectroscópicos.A new natural quaternary alkaloid, N b -methylvoachalotine (1), was obtained from the root bark of Tabernaemontana laeta together with three dimeric indole alkaloids, conodurine (2), voacamine (3) and tabernamine (4), and the monomeric indole alkaloids 19S-heyneanine (5), coronaridine (6) and voacangine (7). The known triterpenes a-amyrin acetate, b-amyrin acetate, lupeol acetate and taraxasterol acetate and the phytosterol b-sitosterol and its 3-O-b-D-glucoside were also identified. The structures of the compounds were elucidated based on spectroscopic studies.

No abstract

No abstract