BackgroundAlzheimer’s disease (AD) is a neurologically degenerative disorder that affects more than
20 million people worldwide. The selective butyrylcholinesterase (BChE) inhibitors and bivalent
cholinesterase (ChE) inhibitors represent new treatments for AD.FindingsA series of lycorine derivatives (1–10) were synthesized and evaluated for
anti-cholinesterase activity. Result showed that the novel compound
2-O-tert-butyldimethylsilyl-1-O-(methylthio)methyllycorine (7) was
a dual inhibitor of human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) with
IC50 values of 11.40 ± 0.66 μM and 4.17 ± 0.29 μM, respectively. The
structure-activity relationships indicated that (i) the 1-O-(methylthio)methyl substituent
in lycorine was better than the 1-O-acetyl group for the inhibition of cholinesterase; (ii)
the acylated or etherified derivatives of lycorine and lycorin-2-one were more potent against hBChE
than hAChE; and (iii) the oxidation of lycorine at C-2 decreases the activity.ConclusionAcylated or etherified derivatives of lycorine are potential dual inhibitors of hBChE and hAChE.
Hence, further study on the modification of lycorine for ChE inhibition is necessary.
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