Selective dual cholinesterase inhibitors from Aconitum laeve

Abstract

New lycoctonine-type dual cholinesterase inhibitor, swatinine-C (1), along with three known norditerpenoid alkaloids, hohenackerine (2), aconorine (5) and lappaconitine (6) and two synthetically known but phytochemically new benzene derivatives, methyl 2-acetamidobenzoate (3) and methyl 4-[2-(methoxycarbonyl)anilino]-4-oxobutanoate (4), was isolated from the roots of A. laeve. Structures of new and known compounds (1–6) were established on the basis of latest spectroscopic techniques and by close comparison with the data available in literature. In vitro, compounds (1–6) were tested against AChE and BChE inhibitory activities. Compounds 1 and 2 showed competitive inhibition against AChE (IC₅₀= 3.7 μM, 4.53 μM) and BChE (IC₅₀= 12.23 μM, 9.94 μM), respectively. Compounds 5 and 6 showed promising noncompetitive type of inhibitory profile against AChE (IC₅₀= 2.51 and 6.13 μM) only. Compounds 3 and 4 showed weak inhibitory profile against both AChE and BChE.

Keywords:

• Aconitum laeve
• diterpenoid alkaloids
• swatinine-C
• methyl 2-acetamidobenzoate
• methyl-4-[2-(methoxycarbonyl)anilino]-4-oxobutanoate
• acetyl cholinesterase (AChE) & butyrylcholinesterase (BChE) inhibition

Acknowledgements

Higher Education commission of Pakistan is hereby acknowledged for providing financial support through HEC, NRPU Research project No. 20-3536.