L-Hypaphorine And D-Hypaphorine: Specific Antiacetylcholinesterase Activity In Rat Brain Tissue

Acetylcholinesterase (AChEis) inhibitors are used to treat neurodegenerative diseases like Alzheimer's disease (AD). L-Hypaphorine (L-HYP) is a natural indole alkaloid that has been shown to have effects on the central nervous system (CNS). The goal of this research was to synthesize L-HYP and D-HYP and test their anticholinesterasic properties in rat brain regions. L-HYP suppressed acetylcholinesterase (AChE) activity only in the cerebellum, whereas D-HYP inhibited AChE activity in all CNS regions studied. No cytotoxic effect on normal human cells (HaCaT) was observed in the case of L-HYP and D-HYP although an increase in cell proliferation. Molecular modeling studies revealed that D-HYP and L-HYP have significant differences in their binding mode positions and interact stereospecifically with AChE's amino acid residues.