Selective dual cholinesterase inhibitors from Aconitum laeve

Area of Science:

• Natural Product Chemistry
• Pharmacology
• Medicinal Chemistry

Background:

• Aconitum species are a rich source of bioactive alkaloids.
• Cholinesterase inhibitors are crucial for treating neurodegenerative diseases like Alzheimer's.

Purpose of the Study:

• To isolate and characterize novel compounds from A. laeve roots.
• To evaluate the in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of isolated compounds.

Main Methods:

• Phytochemical investigation of A. laeve roots using spectroscopic techniques.
• Isolation of six compounds: swatinine-C (1), hohenackerine (2), methyl 2-acetamidobenzoate (3), methyl 4-[2-(methoxycarbonyl)anilino]-4-oxobutanoate (4), aconorine (5), and lappaconitine (6).
• In vitro enzyme inhibition assays to determine AChE and BChE inhibitory activities and mechanisms.

Main Results:

• Swatinine-C (1), a novel lycoctonine-type alkaloid, was identified.
• Compounds 1 and 2 exhibited competitive inhibition against AChE and BChE.
• Compounds 5 and 6 displayed non-competitive inhibition against AChE with low IC50 values.
• Compounds 3 and 4 showed weak inhibitory effects on both enzymes.

Conclusions:

• A. laeve roots contain diverse alkaloids with significant cholinesterase inhibitory potential.
• Swatinine-C and other isolated alkaloids demonstrate promising activity against AChE and BChE, warranting further investigation for therapeutic applications.