Chelerythrine is a benzophenanthridine alkaloid isolated from the root of Zanthoxylum simulans, Chelidonium majus L., and other Papaveraceae. It has a role as an EC 2.7.11.13 (protein kinase C, PKC-alpha/-beta) inhibitor, an antibacterial agent and an antineoplastic agent. It is a benzophenanthridine alkaloid and an organic cation. IC50 ACHE 1.45 muM (1.22-1.71) BChE 8.58 muM (5.34-12.1)
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Title: Simple analogues of natural product chelerythrine: Discovery of a novel anticholinesterase 2-phenylisoquinolin-2-ium scaffold with excellent potency against acetylcholinesterase Zhou B, Li H, Cui Z, Li D, Geng H, Gao J, Zhou L Ref: Eur Journal of Medicinal Chemistry, 200:112415, 2020 : PubMed
As simple analogues of the natural compound chelerythrine, a novel anti-cholinesterase 2-phenylisoquinolin-2-ium scaffold was designed by structure imitation. The activity evaluation led to the discovery of seven compounds with potent anti-acetylcholinesterase activity with IC50 values of
The presented project started by screening a library consisting of natural and natural based compounds for their acetylcholinesterase AChE and butyrylcholinesterase BChE inhibitory activity Active compounds were chemically clustered into groups and further tested on the human cholinesterases isoforms The aim of the presented study was to identify compounds that could be used as leads to target two key mechanisms associated with the AD's pathogenesis simultaneously cholinergic depletion and beta amyloid Abeta aggregation Berberin palmatine and chelerythrine chemically clustered in the so-called isoquinoline group showed promising cholinesterase inhibitory activity and were therefore further investigated Moreover the compounds demonstrated moderate to good inhibition of Abeta aggregation as well as the ability to disaggregate already preformed Abeta aggregates in an experimental set-up using HFIP as promotor of Abeta aggregates Analysis of the kinetic mechanism of the AChE inhibition revealed chelerythrine as a mixed inhibitor Using molecular docking studies it was further proven that chelerythrine binds on both the catalytic site and the peripheral anionic site PAS of the AChE In view of this we went on to investigate its effect on inhibiting Abeta aggregation stimulated by AChE Chelerythrine showed inhibition of fibril formation in the same range as propidium iodide This approach enabled for the first time to identify a cholinesterase inhibitor of natural origin-chelerythrine-acting on AChE and BChE with a dual ability to inhibit Abeta aggregation as well as to disaggregate preformed Abeta aggregates This compound could be an excellent starting point paving the way to develop more successful anti-AD drugs.
Title: 8-hydroxydihydrochelerythrine and 8-hydroxydihydrosanguinarine with a potent acetylcholinesterase inhibitory activity from Chelidonium majus L Cho KM, Yoo ID, Kim WG Ref: Biol Pharm Bull, 29:2317, 2006 : PubMed
Ethanol extract of the aerial portion of Chelidonium majus L. inhibited acetylcholinesterase (AChE) activity without a significant inhibition of butyrylcholinesterase (BuChE). Using mass spectrometry and NMR studies, three active constituents were isolated and identified: 8-hydroxydihydrochelerythrine (1), 8-hydroxydihydrosanguinarine (2), and berberine (3). Compounds 1-3 showed potent inhibitory activity against AChE, with IC50 (microM) values of 0.61-1.85. Compound 1 exhibited competitive and selective inhibition for AChE.
