Research of oxime-CB(7) complexes for central nervous system penetration of quaternary acetylcholinesterase reactivator

Acetylcholinesterase (AChE; E.C. 3.1.1.7) reactivators (also known as oximes) are representatives of the class of antidotes that may be used in the therapy of pesticide or nerve agent poisoning (OPs). Their effectiveness is limited by a low penetration through biological barriers. Oximes are highly hydrophilic compounds since quaternary nitrogen and hydrophilic oxime groups are included in their structure. On the other hand, the preservation of these components in the structure is essential for the reactivation effect.
The main aim of this project is to improve the oxime delivery into cucurbit[7] urils (CB[7]) via encapsulation. Oximes@CB[7] complexes should increasingly overcome the blood-brain barrier and thus diminish the OPs central effect with a subsequent pathologic cascade. In our project, we will comprehensively assess the impact of the oximes@CB[7] complexation on the in vitro and in vivo toxicity, pharmacokinetics profile (absorption, elimination, and brain targeting), safety, and antidotal effectiveness. The research results may be subsequently used in further pre-clinical anti-OPs research.