Recent progress in the identification of selective butyrylcholinesterase inhibitors for Alzheimer's disease

Li, Qi; Yang, Hongyu; Chen, Yao; Sun, Haopeng

doi:10.1016/j.ejmech.2017.03.062

Cited by 263 publications

(144 citation statements)

References 142 publications

Supporting

Mentioning

138

Contrasting

Unclassified

Order By: Relevance

“…Therefore, the development of compounds that can act on both AChE and BChE is of utmost importance. [16] Glutathione-S-transferases are another interesting target for ruthenium-based complexes. Mammalian GSTs occur in several forms, and act on hydrophobic molecules, thus allowing their biotransformation and the detoxification of xenobiotic compounds.…”

Section: Introductionmentioning

confidence: 99%

Organoruthenium Prodrugs as a New Class of Cholinesterase and Glutathione‐S‐Transferase Inhibitors

et al. 2018

View full text Add to dashboard Cite

A small library of 17 organoruthenium compounds with the general formula [Ru (fcl)(chel)(L)] (in which fcl=face capping ligand, chel=chelating bidentate ligand, and L=monodentate ligand) were screened for inhibitory activity against cholinesterases and glutathione-S-transferases of human and animal origins. Compounds were selected to include different chelating ligands (i.e., N,N-, N,O-, O,O-, S,O-) and monodentate ligands that can modulate the aquation rate of the metal species. Compounds with a labile ruthenium chloride bond that provided rapid aquation were found to inhibit both sets of enzymes in reversible competitive modes and at pharmaceutically relevant concentrations. When applied at concentrations that completely abolish the activity of human acetylcholinesterase, the lead compound [(η -p-cymene)Ru(pyrithionato)Cl] (C1 a) showed no undesirable physiological responses on the neuromuscular system. Finally, C1 a was not cytotoxic against non-transformed cells at pharmaceutically relevant concentrations.

show abstract

Section: Introductionmentioning

confidence: 99%

Organoruthenium Prodrugs as a New Class of Cholinesterase and Glutathione‐S‐Transferase Inhibitors

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In recent years, numerous studies have indicated that apart from AChE, the other cholinesterase enzyme, BChE also play a vital role in the progression of AD (Darvesh, 2016;Lane et al, 2006;Li, Yang, Chen, & Sun, 2017). It has been stated that during advanced stages of AD, the level of BChE is maintained constant or may increase in the regions of brain which are involved in cognitive functions even when there is a worrying downfall in the levels of AChE (Greig, Lahiri, & Sambamurti, 2002;Reid & Darvesh, 2015;Tasker, Perry, & Ballard, 2005).…”

Section: Screening Of Nps For Inhibition Of Ache and Bchementioning

confidence: 99%

Identification of embelin, a 3‐undecyl‐1,4‐benzoquinone from Embelia ribes as a multitargeted anti‐Alzheimer agent

Nuthakki

Sharma

Kumar

et al. 2019

Drug Development Research

View full text Add to dashboard Cite

Beta-secreatse (BACE-1) and cholinesterases are clinically validated targets of Alzheimer's disease (AD), for which natural products have provided immense contribution.The multifaceted nature of AD signifies the need of multitargeted agents to tackle this disease. In the search of new natural products as dual BACE-1/cholinesterase inhibitors, a library of pure natural products was screened for inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE-1. The screening efforts have identified 1,4-benzoquinone "embelin," a natural product derived from Embelia ribes displaying inhibition of all three enzymes, with IC 50 values of 2.5, 5.4, and 2.1 μM, respectively. This screen has also identified isoquinoline alkaloids papaverine and L-tetrahydropalmatine as AChE inhibitors. Kinetic study has shown that embelin inhibits EeAChE and EqBChE with ki values of 4.59 and 0.57 μM, in an uncompetitive and noncompetitive manner, respectively. The interactions of embelin with allosteric peripheral anionic site of cholinesterases, has further supported the results of kinetic study. Embelin has also enhanced the activity of P-gp in LS-180 cells, the efflux pump which is involved in the clearance of amyloid-β from AD brain. Further, the cell viability study in neuronal cell line has indicated the excellent therapeutic window of embelin. These results are indicative of the fact that embelin is a multitargeted agent playing role in stopping the formation of amyloid-β oligomers (via inhibition of BACE-1), improves cholinergic-transmission (via inhibition of AChE/BChE) and increases amyloid-β clearance (via P-gp induction). K E Y W O R D Sacetylcholinesterase, Alzheimer's disease, BACE-1, butyrylcholinesterase, embelin, papaverine, L-tetrahydropalmatine

show abstract

“…We subsequently introduced the hydroxy group (33)(34) to the cinnamic acid moiety. Such substitution was favourable for AChE inhibition, the two compounds exhibited a good selectivity on AChE.…”

Section: Ches Inhibitory Activity and Sar Analysismentioning

confidence: 99%

“…The two proteins share an almost 65% homologic amino acid sequences. Catalytic triads in CAS of hAChE and hBuChE consist of conserved amino acids: Ser203, His447, Glu334 in hAChE and Ser198, His438, Glu325 in hBuChE 34 . PAS of hAChE is proved to be closely related to both hydrolysis of ACh and neurotoxic cascade of AD through AChE-induced b-amyloid (Ab) aggregation 35 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer’s disease

Chen

Zhu

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Recent progress in the identification of selective butyrylcholinesterase inhibitors for Alzheimer's disease

Cited by 263 publications

References 142 publications

Organoruthenium Prodrugs as a New Class of Cholinesterase and Glutathione‐S‐Transferase Inhibitors

Organoruthenium Prodrugs as a New Class of Cholinesterase and Glutathione‐S‐Transferase Inhibitors

Identification of embelin, a 3‐undecyl‐1,4‐benzoquinone from Embelia ribes as a multitargeted anti‐Alzheimer agent

Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer’s disease

Contact Info

Product

Resources

About