Inhibition of acetylcholinesterase by thiamine. A structure-function study

Abstract

Eighteen compounds related to thiamine were assayed for their inhibitory potency against electric eel acetylcholinesterase at pH 7.00 and 8.25 by Ellman's method. Data in the form of progress curves were fitted to the integrated form of the rate equation for linear, mixed-type Michaelis-Menten kinetics. The values of Ki thus obtained were compared in order to define the loci of inhibition on the thiamine molecule. It was found that the positively charged quaternary nitrogen atom is the primary locus of inhibition, while alkyl groups in the molecule play a secondary role through hydrophobic association with the enzyme. Protonation of the inhibitors was seen to be an important factor.

Synthesis and biological evaluation of some thiazole derivatives as new cholinesterase inhibitors

“…In a previous work, the inhibition of AChE by thiamine and its derivatives was investigated and structureactivity relationship study was also carried out to identify structural features that are associated with the inhibitory potency of these compounds 16 . Some researchers also carried out considerable research for novel cholinesterase inhibitors bearing amide and hydrazide moieties previously 17 .…”

“…Compounds bearing thiazole moiety have been reported to exhibit a wide spectrum of biological effects including anticholinesterase activity [10][11][12][13][14][15][16] . …”

N-Phenacylthiazolium Salts as Inhibitors of Cholinesterases

“…Vitamin B1 (thiamine) and its derivatives are important regulators of metabolic processes in the central nervous system [33,34] possessing a weak inhibitory action on cholinesterases [35].…”

O-Substituted N(3)-benzyl analogs of vitamin B1 as inhibitors of acetylcholinesterase or butyrylcholinesterase

“…1) and some thiazolium salts were reported to have only weak inhibitory effects on AChE. 25 Our interest in searching for effective inhibitors of both AChE and BChE has been focused on O-substituted structural analogues of thiamine (compounds 3, Fig. 1).…”