engleski

Quinuclidinium derivatives as inhibitors of cholinesterases and reactivators of the phosphylated enzymes

Quinuclidinium derivatives alone, or bound to imidazolium or pyridinium, are reversible inhibitors of cholinesterases and act as protectors of cholinesterases in inhibition by organophosphorus compounds (OP). Most of them are not very strong inhibitors. However, their protection characteristics indicate binding of the compounds to the catalytic and peripheral sites of the cholinesterases which makes them more efficient than one could expect on the basis of the relatively low affinity for the enzymes. Quinuclidinium derivatives with an oxime group were efficient as reactivators of cholinesterases inhibited by organophosphorus compounds. Some carbamoylated quinuclidinium oximes although poor reactivators of OP inhibited acetylcholinesterase, were efficient in the therapy of animals poisoned by soman and tabun. On the other hand, a quinuclidinium derivative coupled with pyridinium oxime was reported as a reactivator of acetylcholinesterase inhibited by soman, but was not particularly efficient in the therapy in soman poisoning. Further studies might clarify some possible contradictions in structure-activity relationship of these compounds. Quniuclidinium-3-ol derivatives are chiral compounds and the stereoselective cholinesterases revealed some preferences for their enantiomers. Studies concerning reactivation of the inhibited cholinesterases and protection against OP in vitro and in vivo were done mainly with racemic quinuclidinium compounds. We review our own results on quinuclidinium compounds as well as those from the literature and highlight the most perspective compounds as protectors and reactivators that should be studied in more details and with respect to the stereoselectivity of cholinesterases. Keywords: Organophosphorus compounds, oximes, protectors, stereoselectivity of cholinesterases

organophosphorus compounds; oximes; protectors; stereoselectivity of cholinesterases

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