Biomolecules, Год журнала: 2024, Номер 14(5), С. 588 - 588

Опубликована: Май 15, 2024

Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross blood–brain barrier, and has demonstrated excellent safety tolerability properties in clinical research. These characteristics indicate it may serve as centrally active ligand of acetylcholinesterase (AChE) butyrylcholinesterase (BChE), whose disruption activity organophosphate compounds (OP) leads uncontrolled excitation potentially life-threatening symptoms. To evaluate olesoxime binding reactivator human AChE BChE, we conducted vitro kinetic studies metabolite insecticide parathion, paraoxon, warfare nerve agents sarin, cyclosarin, tabun, VX. Our results showed that both enzymes possessed affinity for mid-micromolar range, higher than antidotes use (i.e., 2-PAM, HI-6, etc.). While weak reactivate AChE, cyclosarin-inhibited BChE was reactivated overall reactivation rate constant comparable standard HI-6. Moreover, combination maximum increased by 10–30% cyclosarin- sarin-inhibited BChE. Molecular modeling revealed productive interactions between highlighting BChE-targeted therapy. might be added OP poisoning treatment increase efficacy reactivation, its scaffold could provide basis development novel antidotes.

Язык: Английский