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<p>Cholinesterase (ChE) refers to a group of enzymes that play a critical role in the hydrolysis of choline-based esters, particularly acetylcholine, a key neurotransmitter presents in the nervous system. The two types of cholinesterase are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), each with distinct functions and locations found within the body. Cholinesterase inhibitors (ChEIs) have been utilized to treat Alzheimer’s disease (AD). AD is a progressive neurodegenerative disorder characterized by memory loss, impacting on the quality of life. Many studies have highlighted the potential of alkaloids as inhibitors of cholinesterase enzymes. There are various alkaloids which have potential to treat AD with their different modes of actions. This review summarizes more than 14 well-known alkaloids possessing six-membered N-heterocycles as AChE and BuChE inhibitors, such as berberine, boldine, crytolepine, harmine, huperzine A, 6-hydroxycrinamine, nicotine, piperine, salsoline, skimmianine, trigonelline, valerianofal A, 7′-multijuguinone, and 12′-hydroxy-7′-multijuguinone, hamayne, and lycorine.</p> Graphical abstract <p></p>

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Six-membered N-heterocyclic alkaloids as ChE inhibitors in alzheimer’s disease treatment

  • 期刊论文

  • 发表日期：

    2025年11月6日

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  • Parul Yadav,
  • Anchal Dabas,
  • Ram Singh

摘要

Cholinesterase (ChE) refers to a group of enzymes that play a critical role in the hydrolysis of choline-based esters, particularly acetylcholine, a key neurotransmitter presents in the nervous system. The two types of cholinesterase are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), each with distinct functions and locations found within the body. Cholinesterase inhibitors (ChEIs) have been utilized to treat Alzheimer’s disease (AD). AD is a progressive neurodegenerative disorder characterized by memory loss, impacting on the quality of life. Many studies have highlighted the potential of alkaloids as inhibitors of cholinesterase enzymes. There are various alkaloids which have potential to treat AD with their different modes of actions. This review summarizes more than 14 well-known alkaloids possessing six-membered N-heterocycles as AChE and BuChE inhibitors, such as berberine, boldine, crytolepine, harmine, huperzine A, 6-hydroxycrinamine, nicotine, piperine, salsoline, skimmianine, trigonelline, valerianofal A, 7′-multijuguinone, and 12′-hydroxy-7′-multijuguinone, hamayne, and lycorine.

Graphical abstract