Naslov
Novel oximes in counteracting organophosphates exposure

Autori
Kovarik, Zrinka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract book of the 17th Medical Chemical Defense Conference "Chemical Warfare Agents - old problems and new challenges" / - München, 2019, 22-22

Skup
17th Medical Chemical Defense Conference "Chemical Warfare Agents - old problems and new challenges"

Mjesto i datum
München, Njemačka, 27.03.2019. - 28.03.2019

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
nerve agents ; reactivators ; acetylcholinesterase

Sažetak
Organophosphates (OP) known as nerve agents (soman, sarin, tabun, VX) present a threat in terrorist attacks and conflicts, as was the case recently in Syria, Malesia and UK. The main targets of OP compounds are acetylcholinesterase (AChE), the essential enzyme in neurotransmission, and butyrylcholinesterase, its back-up enzyme. However, the antidotes currently in use, which act as reactivators of inhibited AChE, were empirically synthesized before the two enzyme’s crystal structures were resolved. Due to structural requirements, their binding affinity and reactivation rate have not been well-balanced. Our computational and experimental studies of both cholinesterase interactions with a wide range of ligands defined favourable characteristic for potential new antidotes, and directed the subsequent synthesis of selected leads. Thorough in vitro and in vivo experimental evaluation demonstrated a feasible approach to the development of an oxime-assisted catalytic bioscavengers of soman, tabun and VX based on an efficient reactivation of cholinesterases. Ultimately, the oxime-assisted catalytic scavenging of the nerve agents in mice improved therapeutic outcomes preventing lethality and resulted in a delayed onset of toxicity symptoms. Acknowledgment: This work was supported by the Croatian Science Foundation (HrZZ-IP-2018-01-7683).

Izvorni jezik
Engleski

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