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• W2068815520 abstract "Previous kinetic studies investigating the interactions between human acetylcholinesterase (AChE), structurally different organophosphorus compounds (OP) and oximes did not reveal a conclusive structure–activity relationship of the different reactions. The only exception was for a homologous series of methylphosphonofluoridates bearing C1–C4 O-n- or O-i-alkyl residues. Hence, it was tempting to investigate the kinetic interactions between different pentylsarin analogues, human AChE and two oximes, obidoxime and HI 6, in order to increase the understanding of structure–activity relationship between highly toxic OP and human AChE. The rate constants for the inhibition of human erythrocyte AChE by four pentylsarin compounds (ki), for the spontaneous dealkylation (aging, ka) and reactivation (ks) of inhibited AChE as well as for the oxime-induced reactivation of inhibited AChE by obidoxime and HI 6 reflected by the dissociation constant (KD) and the reactivity constant (kr) were determined. All pentylsarin analogues had a high inhibitory potency towards AChE. Inhibited AChE was subject to spontaneous reactivation which outweighed aging substantially. Pentylsarin-inhibited AChE could be reactivated by oximes, HI 6 being more potent than obidoxime. The determination of inhibition, reactivation and aging kinetics of pentylsarin analogues with human AChE extends the database on interactions between AChE and methylphosphonofluoridate homologues with C1–C4 n- and i-alkyl residues demonstrating a structure–activity relationship depending on the chain length with certain differences regarding inhibition and post-inhibitory reactions. Unfortunately, no structure–activity relationship could be observed for the oxime-induced reactivation of inhibited AChE. In view of previous results with numerous structurally different organophosphates, organophosphonates and phosphoramidates it has to be concluded that up to now kinetic studies did not provide decisive information for the development of more effective oxime-based reactivators." @default.
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• W2068815520 date "2009-06-01" @default.
• W2068815520 modified "2023-10-06" @default.
• W2068815520 title "Interaction of pentylsarin analogues with human acetylcholinesterase: A kinetic study" @default.
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• W2068815520 doi "https://doi.org/10.1016/j.toxlet.2009.02.010" @default.
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