Abstract
During a research program to identify new cholinesterase inhibitors of natural origin, two new 7,8-didehydroprotoberberine alkaloids (1 and 2) and nine known compounds (3–11) were isolated from the capsules of the common ornamental poppy, Papaver setiferum (previously P. pseudo-orientale). Despite their reported instability, the 7,8-didehydroprotoberberines isolated herein appeared relatively stable, particularly as their trifluoroacetic acid salts. The spatial distributions of the isolated alkaloids were also analyzed using desorption electrospray ionization imaging mass spectrometry. The alkaloids were localized predominantly within the walls and vascular bundles of the capsules, with the highest relative abundances occurring in the lower half of the capsules toward the peduncle. The relative abundances of the alkaloids were also compared across plant development stages. Although most alkaloids did not show clear patterns in their concentration across development stages, the concentration of suspected oxidation products clearly spiked upon plant death. Finally, all isolated natural products were screened for inhibitory activities against a panel of cholinesterases, from both human and animal sources. These studies identified several competitive inhibitors of cholinesterases with potency in the low micromolar range (1–4, 6, 7), offering new lead compounds for the development of cholinesterase inhibitory drugs.
Highlights
During a research program to identify new cholinesterase inhibitors of natural origin, two new 7,8-didehydroprotoberberine alkaloids (1 and 2) and nine known compounds (3−11) were isolated from the capsules of the common ornamental poppy, Papaver setiferum
Drugs with cholinesterase inhibitory activity prolong the lifetime of acetylcholine, resulting in improvement of cholinergic function and alleviation of symptoms.[6,9−11] AChE inhibitors are used in the treatment of myasthenia gravis, a long-term neuromuscular disease.[1,8]
The anionic site binds to the quaternary ammonium ion of acetylcholine through cation−π interactions, while the esteratic site is responsible for ester hydrolysis.[12]
Summary
During a research program to identify new cholinesterase inhibitors of natural origin, two new 7,8-didehydroprotoberberine alkaloids (1 and 2) and nine known compounds (3−11) were isolated from the capsules of the common ornamental poppy, Papaver setiferum (previously P. pseudo-orientale). Extraction of dried P. setiferum capsules with MeOH/CH2Cl2 followed by reversed-phase HPLC led to the isolation of two new protoberberine alkaloids as their TFA salts (1 and 2) (Figure 1).
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