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Molecular modeling and docking calculations of 4-acyloxy-biphenyl-4′-N-butylcarbamates as potential inhibitors of human butyrylcholinesterase
- Source :
- Canadian Journal of Chemistry. 94:72-77
- Publication Year :
- 2016
- Publisher :
- Canadian Science Publishing, 2016.
-
Abstract
- The kinetic studies and drug designs of butyrylcholinesterase play an important role in the development of Alzheimer’s disease therapeutics. In this research, automated docking studies were performed to provide useful insights into butyrylcholinesterase inhibition binding modes with designed 4-acyloxy-biphenyl-4′-N-butylcarbamates (compounds 1–8). Moreover, several significant linear correlations between experimental and calculated docking results are observed. Among compounds 1–7, compound 3, which exhibits the strongest hydrophobicity and has four carbonyl hydrogen bindings, shows the highest binding affinity (Ki = 1.4 μmol/L) with a binding energy of −7.99 kcal/mol. The observed linear correlation of experimental and calculated inhibition constants (Ki) indicates that the molecular docking results are reliable. Moreover, a good linear correlation is observed between calculated binding energies and experimental pKi. The experimental Hansch hydrophobicity constants (π values) are also correlated with the docked binding energy. This study reveals important correlations between butyrylcholinesterase experimental and docking results that contribute to the kinetic based identification of antagonists for the treatment of Alzheimer’s disease. Furthermore, these docked models provide important insights into a potential series of 4,4′-biphenol-based inhibitors of butyrylcholinesterase.
- Subjects :
- Biphenyl
Molecular model
010405 organic chemistry
Stereochemistry
Organic Chemistry
Binding energy
General Chemistry
01 natural sciences
Catalysis
0104 chemical sciences
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
chemistry
Docking (molecular)
Cholinergic neurotransmission
Linear correlation
030217 neurology & neurosurgery
Butyrylcholinesterase
Subjects
Details
- ISSN :
- 14803291 and 00084042
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- Canadian Journal of Chemistry
- Accession number :
- edsair.doi...........4905b91d59dba337b9c27440b3461211