engleski

Nerve agent bioscavengers based on an efficient oxime-assisted reactivation of cholinesterases

Poisoning caused by the nerve agents (NA) calls for immediate treatment, which usually consists of a combined administration of an anticholinergic drug and an aldoxime as the reactivator of acetylcholinesterase (AChE). Newly considered strategies in medical protection against NA focus on the use of exogenously administered butyrylcholinesterase (BChE). The overall idea is to administer such an enzyme in combination with a specific aldoxime, to scavenge NA before it can reach and inhibit synaptic AChE. Recently we demonstrated through a combination of in silico, in vitro, ex vivo, and in vivo results, a feasible approach to the development of an oxime-assisted catalytic bioscavenger of NA based on the efficient reactivation of cholinesterases. Additionally, several novel aldoximes selected as efficient reactivators of NA-inhibited cholinesterases possessed enhanced central nervous system penetration capabilities, and as such present centrally acting reactivators. Our findings offer a platform for further antidote and scavenger development for exposure to organophosphates. Acknowledgments: This work was supported by the Croatian Science Foundation (HrZZ-IP-2018-01-7683).

acetylcholinesterase, bioscavenger, nerve agents

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