Naslov
Inhibition of acetylcholinesterase by three new pyridinium compounds and their effect on phosphylation of the enzyme

Autori
Škrinjarić-Špoljar, Mira ; Burger, Nicoletta ; Buntić, Anđelka

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

Izvornik
Proceedings of the CB Medical Treatment Symposium: An Exploration of Present Capabilities and Future Requirements, The Second Chemical and Biological Medical Treatment Symposium, Spiez, Švicarska, 1966 / Price, Barbara - Portland (ME) : Price R., Applied Science and Analysis, ASA, SAD, 1997

Skup
The Second Chemical and Biological Medical Treatment Symposium, Spiez 1996, Švicarska

Mjesto i datum
Spiez, Švicarska, 07.07.1996. - 12.07.1996

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
benzoyl-pyridinium compounds; mono-pyridinium compounds; acetylcholinesterase; reversible inhibition; soman; VX; protection; reactivation

Sažetak
Three new compounds of the benzoyl-pyridinium type were prepared: 1-phenacyl-2-methylpyridinium chloride (1), 1-benzoylethyl-pyridinium chloride (2) and 1-benzoylethylpyridinium-4-aldoxime chloride (3) and assayed in vitro for their inhibitory effect on human blood acetylcholinesterase (AChE). All the three compounds inhibited AChE reversibly ; compound 1 was found to bind to both enzyme binding sites, compound 2 was bound to the catalytic site and compound 3 to the allosteric site. The binding affinity of the compounds for the enzyme was compared with their protective effect (PI) in AChE phoshonylation by soman and VX. PI was evaluated from phosphonylation measured in the absence and in presence of the compounds, which were applied in concentrations corresponding to the values of their enzyme/inhibitor dissociation constants for binding of the inhibitor to the catalytic and/or allosteric binding sites on the enzyme. PI was also calculated from theoretical equations deduced from the reversible inhibition of the enzyme. The compounds 1 and 3 protected the enzyme from phosphonylation by soman and VX, whereas no protection was observed in the presence of compound 2 under the same conditions. Irrespective of the binding sites to AChE, PI for compounds 1 and 3 evaluated from phosphonylation agreed with PI calculated from reversible inhibition. The oxime compound 3 was found to be a weak reactivator of methylphosphonylated AChE.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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