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 Nb-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.
Highlights
The year 2006 marked a century since the first description of Alzheimer’s disease (AD) by Alois Alzheimer
Whereas several new natural and synthetic compounds are reported in the scientific literature as cholinesterase inhibitors (ChEI) candidates, this research is continuously improved as better drugs for AD is still required
The less polar fractions observed in thin layer chromatography (TLC) were chosen for Gas chromatography-mass spectrometry (GC-MS) analysis
Summary
The year 2006 marked a century since the first description of Alzheimer’s disease (AD) by Alois Alzheimer. AD, The etiology of AD is not very clear and multiple factors, such as amyloid-β peptide (Aβ) and tau protein aggregation, excessive transition metals, oxidative stress and reduced acetylcholine (ACh) level, have been implicated (Ji and Zhang 2006). It is a cholinergic deficiency rather than other neurochemical deficits that is thought to play a pivotal role in the development of AD symptoms (Farlow 2002). Whereas several new natural and synthetic compounds are reported in the scientific literature as cholinesterase inhibitors (ChEI) candidates, this research is continuously improved as better drugs for AD is still required. Within the structure diversity of the ChEI, plant alkaloids are the most studied already leading to the development of new drugs (e.g. galanthamine, huperzine and phenserines) (Houghton et al 2006, Mukherjee et al 2007)
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