Nalazite se na CroRIS probnoj okolini. Ovdje evidentirani podaci neće biti pohranjeni u Informacijskom sustavu znanosti RH. Ako je ovo greška, CroRIS produkcijskoj okolini moguće je pristupi putem poveznice www.croris.hr
izvor podataka: crosbi

Pyridinium oximes with ortho-positioned chlorine moiety exhibit improved physico- chemical properties and efficient reactivation of human acetylcholinesterase inhibited by several nerve agents (CROSBI ID 254945)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Zorbaz, Tamara ; Malinak, David ; Maraković, Nikola ; Maček Hrvat, Nikolina ; Zandona, Antonio ; Novotny, Michal ; Skarka, Adam ; Andrys, Rudolf ; Benkova, Marketa ; Soukup, Ondrej et al. Pyridinium oximes with ortho-positioned chlorine moiety exhibit improved physico- chemical properties and efficient reactivation of human acetylcholinesterase inhibited by several nerve agents // Journal of medicinal chemistry, 61 (2018), 23; 10753-10766. doi: 10.1021/acs.jmedchem.8b01398

Podaci o odgovornosti

Zorbaz, Tamara ; Malinak, David ; Maraković, Nikola ; Maček Hrvat, Nikolina ; Zandona, Antonio ; Novotny, Michal ; Skarka, Adam ; Andrys, Rudolf ; Benkova, Marketa ; Soukup, Ondrej ; Katalinić, Maja ; Kuca, Kamil ; Kovarik, Zrinka ; Musilek, Kamil

engleski

Pyridinium oximes with ortho-positioned chlorine moiety exhibit improved physico- chemical properties and efficient reactivation of human acetylcholinesterase inhibited by several nerve agents

Six chlorinated bispyridinium mono-oximes, analogous to potent charged reactivators K027, K048, and K203, were synthesized with the aim of improving lipophilicity and reducing the pKa value of the oxime group, thus resulting in a higher oximate concentration at pH 7.4 compared to non-chlorinated analogues. The nucleophilicity was examined and the pKa was found to be lower than that of analogous non- chlorinated oximes. All the new compounds efficiently reactivated human AChE inhibited by nerve agents cyclosarin, sarin, and VX. The most potent was the bis-chlorinated analogue of oxime K027 with significantly improved ability to reactivate the conjugated enzyme due to improved binding affinity and molecular recognition. Its overall reactivation of sarin-, VX-, and cyclosarin-inhibited AChE was respectively, three-, seven-, and eight-fold higher than by K027. Its universality, favorable acid dissociation constant coupled with its negligible cytotoxic effect and successful ex vivo scavenging of nerve agents in whole human blood warrant further analysis of this compound as an organophosphorus antidote.

organophosphorus compound, cholinesterase, antidote, pralidoxime, asoxime, chlorinated pyridinium oxime

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o izdanju

61 (23)

2018.

10753-10766

objavljeno

0022-2623

1520-4804

10.1021/acs.jmedchem.8b01398

Povezanost rada

Farmacija, Kemija, Temeljne medicinske znanosti

Poveznice
Indeksiranost