Debord_2002_J.Enzyme.Inhib.Med.Chem_17_197

Reference

Title : Inhibition of butyrylcholinesterase by phenothiazine derivatives - Debord_2002_J.Enzyme.Inhib.Med.Chem_17_197
Author(s) : Debord J , Merle L , Bollinger JC , Dantoine T
Ref : J Enzyme Inhib Med Chem , 17 :197 , 2002
Abstract :

The inhibition of horse serum butyrylcholinesterase (EC 3.1.1.8) by 10 phenothiazine or thioxanthene derivatives was studied with a purified enzyme. Most compounds were mixed inhibitors, but for some of them an apparent competitive inhibition was observed. The competitive inhibition constants (K) were in the range 0.05 to 5 microM. The structures of the inhibitors were modeled by geometry optimization with the AM1 semi-empirical molecular orbital method and octanol/water partition coefficients were estimated with the CLOGP software. Quantitative structure-activity relationships identified lipophilicity, molecular volume, and electronic energies as the main determinants of inhibition. This quantitative model suggested hydrophobic and charge-transfer interactions of the phenothiazine ring with a tryptophan residue at the "anionic" site of the enzyme, and a hydrophobic interaction of the lateral chain with nonpolar amino acids.

PubMedSearch : Debord_2002_J.Enzyme.Inhib.Med.Chem_17_197
PubMedID: 12443046

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Citations formats

Debord J, Merle L, Bollinger JC, Dantoine T (2002)
Inhibition of butyrylcholinesterase by phenothiazine derivatives
J Enzyme Inhib Med Chem 17 :197

Debord J, Merle L, Bollinger JC, Dantoine T (2002)
J Enzyme Inhib Med Chem 17 :197