Aromatic N‐substituted 2‐hydroxyiminoacetamide oximes: preparation, enantioseparation, and interactions with cholinesterases (CROSBI ID 628074)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Šinko, Goran ; Maraković, Nikola ; Knežević, Anamarija ; Vinković, Vladimir ; Kovarik, Zrinka
engleski
Aromatic N‐substituted 2‐hydroxyiminoacetamide oximes: preparation, enantioseparation, and interactions with cholinesterases
We designed and prepared four novel oxime compounds with an N‐substituted 2‐hydroxyiminoacetamide scaffold in order to test their interaction with acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) and their efficacy in reactivation of phosphylated ChEs. 1‐phenylallylamine was prepared from cinnamyl alcohol in an Overman reaction and an azide group was introduced via a three‐step process. The azide group enabled us to prepare more elaborate structures by the copper‐catalysed azide‐alkyne cycloaddition. N‐substituted 2‐ hydroxyiminoacetamides (1 – 4) differ in their peripheral site binding moiety, which ranges from an azide group to functionalized heterocycles. We separated the enantiomers of N‐substituted 2‐hydroxyiminoacetamides using chiral HPLC with high enantiomeric excess (88 % to 99 %). The absolute configuration of the enantiomers was determined by comparing their retention times with N‐substituted 2‐hydroxyiminoacetamides prepared from (S)‐1‐phenyl‐allylamine. All four racemic compounds reversibly inhibited BChE and AChE with inhibition constants ranging from 10 μmol/L to 160 μmol/L and from 30 μmol/L to 900 μmol/L, respectively. All of the compounds displayed a higher preference for binding to BChE, which indicates them as possible candidates for continuous scavenging of organophosphates as BChEoxime pairs. Our preliminary reactivation study on paraoxon‐inhibited BChE shows a reactivation potential for these compounds. We expect that an asymmetrical centre within the molecule will have a beneficial role in the reactivation of cholinesterases inhibited by OP compounds. This work was supported in part by the Croatian Science Foundation (project 4307).
reactivation; cycloadition
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Podaci o prilogu
99-100.
2015.
objavljeno
Podaci o matičnoj publikaciji
12th International Meeting on Cholinesterases and 6th Paraoxonase Conference, Elche, Španjolska, Program
Podaci o skupu
12th International Meeting on Cholinesterases and 6th Paraoxonase Conference
poster
27.09.2015-02.10.2015
Elche, Španjolska