l-Hypaphorine and d-hypaphorine: Specific antiacetylcholinesterase activity in rat brain tissue.
2021
Abstract 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.
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