This review provides a comprehensive account of advances in the field of cholinesterase inhibitors isolated from the Buxaceae family. Naturally occurring anticholinesterases derived from plants are considered to be a potential source of new drug candidates for treating Alzheimer's disease (AD). AD is now universally accepted as an irreversible, incurable, and progressive neurological disorder. Initiating with memory impairment, propagating with cognitive deficit, and ultimately leading to death is the general pathway of AD. Lower level of acetylcholine in the brain is characterized as one of the prominent reasons for AD. The cholinergic hypothesis states that elevated levels of acetylcholine in the brain can alleviate symptoms of AD. Steroidal and terpenoidal alkaloids isolated from plants of the Buxaceae family have been reviewed here for their anticholinesterase activity. Most of them have shown in vitro inhibition of horse serum butyrylcholinesterase (BuChE, EC 3.1.1.7) and electric eel acetylcholinesterase (AChE, EC 3.1.1.8). Although the general consensus has concluded that cholinesterase inhibitors may alleviate AD symptoms but cannot cure the disease, new drugs are still being sought to improve the quality of life of AD patients. Steroidal and terpenoidal anticholinesterase alkaloids can prove to be a promising group of AChE inhibitors.

• Keywords
• Alzheimer’s disease, Buxaceae, acetylcholinesterase, butyrylcholinesterase., cholinesterase inhibitors, inhibition,
• MeSH
• Alzheimer Disease * drug therapy   MeSH
• Cholinesterase Inhibitors * therapeutic use   pharmacology   isolation & purification   MeSH
• Humans MeSH
• Plant Extracts * therapeutic use   chemistry   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Cholinesterase Inhibitors * MeSH
• Plant Extracts * MeSH

Tacrine (THA), the first clinically effective acetylcholinesterase (AChE) inhibitor and the first approved drug for the treatment of Alzheimer's disease (AD), was withdrawn from the market due to its side effects, particularly its hepatotoxicity. Nowadays, THA serves as a valuable scaffold for the design of novel agents potentially applicable for AD treatment. One such compound, namely 7-methoxytacrine (7-MEOTA), exhibits an intriguing profile, having suppressed hepatotoxicity and concomitantly retaining AChE inhibition properties. Another interesting class of AChE inhibitors represents Huprines, designed by merging two fragments of the known AChE inhibitors-THA and (-)-huperzine A. Several members of this compound family are more potent human AChE inhibitors than the parent compounds. The most promising are so-called huprines X and Y. Here, we report the design, synthesis, biological evaluation, and in silico studies of 2-methoxyhuprine that amalgamates structural features of 7-MEOTA and huprine Y in one molecule.

• Keywords
• 2-methoxyhuprine, 7-MEOTA, Alzheimer’s disease, acetylcholinesterase, butyrylcholinesterase, huprine Y, tacrine,
• MeSH
• Acetylcholinesterase MeSH
• Enzyme Activation drug effects   MeSH
• Alzheimer Disease drug therapy   MeSH
• Aminoquinolines chemical synthesis   chemistry   pharmacology   MeSH
• Butyrylcholinesterase MeSH
• Cholinesterase Inhibitors chemistry   pharmacology   MeSH
• Blood-Brain Barrier metabolism   MeSH
• Heterocyclic Compounds, 4 or More Rings chemistry   pharmacology   MeSH
• Hydrolysis MeSH
• Inhibitory Concentration 50 MeSH
• Catalytic Domain MeSH
• Humans MeSH
• Molecular Conformation MeSH
• Models, Molecular MeSH
• Molecular Structure MeSH
• Cell Line, Tumor MeSH
• Drug Discovery * MeSH
• Permeability MeSH
• Drug Design MeSH
• Tacrine analogs & derivatives   chemistry   pharmacology   MeSH
• Protein Binding MeSH
• Binding Sites MeSH
• Cell Survival drug effects   MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 7-methoxytacrine MeSH Browser
• Acetylcholinesterase MeSH
• Aminoquinolines MeSH
• Butyrylcholinesterase MeSH
• Cholinesterase Inhibitors MeSH
• Heterocyclic Compounds, 4 or More Rings MeSH
• huprine Y MeSH Browser
• Tacrine MeSH