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Nantenine as an acetylcholinesterase inhibitor: SAR, enzyme kinetics and molecular modeling investigations.
J Enzyme Inhib Med Chem. 2011 Feb; 26(1):46-55.JE

Abstract

Nantenine, as well as a number of flexible analogs, were evaluated for acetylcholinesterase (AChE) inhibitory activity in microplate spectrophotometric assays based on Ellman's method. It was found that the rigid aporphine core of nantenine is an important structural requirement for its anticholinesterase activity. Nantenine showed mixed inhibition kinetics in enzyme assays. Molecular docking experiments suggest that nantenine binds preferentially to the catalytic site of AChE but is also capable of interacting with the peripheral anionic site (PAS) of the enzyme, thus accounting for its mixed inhibition profile. The aporphine core of nantenine may thus be a useful template for the design of novel PAS or dual-site AChE inhibitors. Inhibiting the PAS is desirable for prevention of aggregation of the amyloid peptide Aβ, a major causative factor in the progression of Alzheimer's disease (AD).

Authors+Show Affiliations

City University of New York Hunter College, Department of Chemistry, New York, NY 10065, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20583856

Citation

Pecic, Stevan, et al. "Nantenine as an Acetylcholinesterase Inhibitor: SAR, Enzyme Kinetics and Molecular Modeling Investigations." Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 26, no. 1, 2011, pp. 46-55.
Pecic S, McAnuff MA, Harding WW. Nantenine as an acetylcholinesterase inhibitor: SAR, enzyme kinetics and molecular modeling investigations. J Enzyme Inhib Med Chem. 2011;26(1):46-55.
Pecic, S., McAnuff, M. A., & Harding, W. W. (2011). Nantenine as an acetylcholinesterase inhibitor: SAR, enzyme kinetics and molecular modeling investigations. Journal of Enzyme Inhibition and Medicinal Chemistry, 26(1), 46-55. https://doi.org/10.3109/14756361003671078
Pecic S, McAnuff MA, Harding WW. Nantenine as an Acetylcholinesterase Inhibitor: SAR, Enzyme Kinetics and Molecular Modeling Investigations. J Enzyme Inhib Med Chem. 2011;26(1):46-55. PubMed PMID: 20583856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nantenine as an acetylcholinesterase inhibitor: SAR, enzyme kinetics and molecular modeling investigations. AU - Pecic,Stevan, AU - McAnuff,Marie A, AU - Harding,Wayne W, Y1 - 2010/06/28/ PY - 2010/6/30/entrez PY - 2010/6/30/pubmed PY - 2011/8/4/medline SP - 46 EP - 55 JF - Journal of enzyme inhibition and medicinal chemistry JO - J Enzyme Inhib Med Chem VL - 26 IS - 1 N2 - Nantenine, as well as a number of flexible analogs, were evaluated for acetylcholinesterase (AChE) inhibitory activity in microplate spectrophotometric assays based on Ellman's method. It was found that the rigid aporphine core of nantenine is an important structural requirement for its anticholinesterase activity. Nantenine showed mixed inhibition kinetics in enzyme assays. Molecular docking experiments suggest that nantenine binds preferentially to the catalytic site of AChE but is also capable of interacting with the peripheral anionic site (PAS) of the enzyme, thus accounting for its mixed inhibition profile. The aporphine core of nantenine may thus be a useful template for the design of novel PAS or dual-site AChE inhibitors. Inhibiting the PAS is desirable for prevention of aggregation of the amyloid peptide Aβ, a major causative factor in the progression of Alzheimer's disease (AD). SN - 1475-6374 UR - https://www.unboundmedicine.com/medline/citation/20583856/Nantenine_as_an_acetylcholinesterase_inhibitor:_SAR_enzyme_kinetics_and_molecular_modeling_investigations_ L2 - https://www.tandfonline.com/doi/full/10.3109/14756361003671078 DB - PRIME DP - Unbound Medicine ER -