Discovery of potent and selective butyrylcholinesterase inhibitors through the use of pharmacophore-based screening

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

“…Moreover, compound 33 could inhibit the self‐aggregation of Aβ 1–42 in a dose‐dependent manner, and it also served as a protective agent against Aβ 1–42 ‐induced toxicity at 5 and 10 µM. Williams et al 198 generated several binding poses of tacrine in BChE crystal structure (PDB ID: 4BDS). One of the binding modes showed that the conformation of tacrine seemed to be relatively close to a hydrophobic pocket that exists in BChE but not in AChE.…”

“…One of the binding modes showed that the conformation of tacrine seemed to be relatively close to a hydrophobic pocket that exists in BChE but not in AChE. Based on this conformation, Williams et al 198 built a pharmacophore model to search selective BChE inhibitors. Compound 34 (Figure 12) displayed no inhibitory activity against ee AChE up to 5 µM, while as expected it inhibited eq BChE with IC 50 value of 0.03 µM, giving a high selectivity and great inhibitory activity.…”

New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors

“…The most well-received hypothesis is the deficit of an important neurotransmitter in the cholinergic neurotransmission, acetylcholine (ACh) 3,[5][6][7] . The deficit of ACh has profound effects on the signaling that involves learning ability and long-term memory [8][9][10] . The cholinesterase enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are accountable for the degradation of ACh through hydrolysis.…”

“…The cholinesterase enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are accountable for the degradation of ACh through hydrolysis. Thus, cholinesterase inhibitors are important drugs in treating AD by maintaining the level of ACh [10][11][12] . AChE predominates in the brain of a healthy person and contributes to ACh hydrolysis in the brain for approximately 80% 7,13 .…”

Butyrylcholinesterase - BuChE: A Potential Target for Development of Drugs for Alzheimer's Disease Treatment

“…73,74 Willians e colaboradores exploraram a combinação de técnicas in silico e in vitro na busca por novos inibidores seletivos de BuChE. 75 Os autores utilizaram a tacrina (2) como protótipo e caracterizaram seu modo de interação com AChE e BuChE através da modelagem molecular. Posteriormente, foram propostas modificações estruturais capazes de potencializar as interações com a BuChE em detrimento da AChE, graças as diferenças entre os respectivos sítios que fazem com que a BuChE acomode melhor a presença de grupamentos mais volumosos e flexíveis.…”