The reactivators of acetylcholinesterase (AChE, EC 184.108.40.206) are very important components in the treatment of intoxications caused by organophosphate inhibitors such as nerve agents and pesticides. These inhibitors covalently bind to active site of mentioned enzyme and irreversibly inhibit its activity. The reactivator breaks the inhibitor-enzyme covalent bond and restores its activity. Unfortunately, there is no reactivator applicable for every type of inhibitor; it means that every structural change in the molecule of inhibitor needs a specific structure of the reactivator. More than 100 compounds was prepared and evaluated in our department since 2004. Some reactivators were able to exceed potency of commercial available compounds in vitro. The SAR study was used to select more active reactivators. The key features of the reactivator’s molecule were determined.
The work was supported by the Grant Agency of Ministry of Education, Youth and Sports (Czech Republic) – grant no. ME865.