In vitro Inactivation of Rat Brain Acetylcholinesterase by DSP-4 and Its Derivatives OS-21 and OS-23 and Protective Activity of Tacrine (9-Amino-1,2,3,4-tetrahydroacridine)

Patočka, Jiří; Jun, Daniel; Kuča, Kamil

doi:10.14712/18059694.2018.42

Acta Medica > Archive > 2005, Vol. 48 > Issue 3-4 > In vitro Inactivation of Rat Brain…

Acta Med. 2005, 48: 145-148

https://doi.org/10.14712/18059694.2018.42

In vitro Inactivation of Rat Brain Acetylcholinesterase by DSP-4 and Its Derivatives OS-21 and OS-23 and Protective Activity of Tacrine (9-Amino-1,2,3,4-tetrahydroacridine)

Jiří Patočka^a,b, Daniel Jun^b,c, Kamil Kuča^b

^aSouth Bohemia University, Faculty of Health and Social Studies, Department of Radiology and Toxicology, Czech Republic
^bUniversity of Defence, Faculty of Military Health Sciences, Department of Toxicology, Czech Republic
^cCharles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové, Czech Republic

Received November 1, 2004
Accepted June 1, 2005

Tertiary N-haloethylamines are able to cyclize to the corresponding aziridinium ions. The inhibitory activity of the DSP-4 (N-(o-brombenzyl)-N-ethyl-2-chlorethylamine) and its two derivatives OS-21 (N-benzyl-N-ethyl-2-chloroethylamine) and OS-23 (N-fenylethyl-N-ethyl-2-chloroethylamine) was studied toward rat brain acetylcholinesterase (AChE) in vitro. The influence of the THA (tacrine; 9–amino-1,2,3,4–tetrahydroacridine) on AChE inhibition by these substances was also evaluated. The results demonstrated that all of three aziridinium compounds formed in solution caused a timeand concentration-dependent irreversible enzyme inhibition. The association of aziridinium compounds with the AChE was a relatively slow second-order reaction. DSP-4 showed the fastest rate of AChE alkylation, OS-21 had a lowered rate and OS-23 displayed the lowest rate. Pretreatment of the enzyme by THA decreased the rate of alkylation by all three aziridinium compounds by allosteric mechanism.