Naslov
Assessing the efficacy of novel uncharged oximes as reactivators of phosphylated cholinesterases

Autori
Katalinić, Maja ; Zorbaz, Tamara ; Maraković, Nikola ; Braïki, Anissa ; Renou, Julien ; Nachon, Florian ; Jean, Ludovic ; Renard, Pierre‐Yves ; Kovarik, Zrinka

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

Izvornik
12th International Meeting on Cholinesterases and 6th Paraoxonase Conference, Elche, Španjolska, Program / - , 2015, 97-98

Skup
12th International Meeting on Cholinesterases and 6th Paraoxonase Conference

Mjesto i datum
Elche, Španjolska, 27.09.2015. - 02.10.2015

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
molecular modelling

Sažetak
A set of newly synthesized uncharged oximes was characterised through detailed in silico and in vitro studies as potential therapy in organophosphorus compound (OP) poisoning. We analysed the oximes’ interaction with cholinesterases (ChE) and assessed their efficacy in reactivating cholinesterases inhibited by different organophosphorus compounds. The results showed that the ChE binding affinity for oximes is comparable to that for similarly charged pyridinium oximes, Ki ranging from 5‐150 μM. The observed reactivation potency was most pronounced in the case of VX‐inhibited ChE, reflected in a high reactivation maximum of 80 % obtained within 5‐60 min. Such a result indicated that the studied uncharged oximes could be considered potential centrally acting antidotes for OP‐poisoning and could be promising candidates for in vivo studies. However, as in the case of the charged oximes, their relatively tight binding to uninhibited ChE could imply their toxicity in vivo. By means of molecular modelling, we analysed the positioning of the tested oximes in the OP‐inhibited ChE active site and evaluated possibilities for further oxime structure refinements. Acknowledgment: This work was supported by the COGITO Croatian‐French bilateral grant (2014‐2015) and CSF (4307).

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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