PMID: 16640027Apr 28, 2006Paper

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)

Acta Medica (Hradec Králové)
Jiri PatockalKamil Kucal

Abstract

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 time- and 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.

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.