Kamil KUCA, Jiri CABAL, Daniel JUN, Martina HRABINOVA, Jiri KASSA

YENİ GELİŞTİRİLEN K027 VE K048 OKSİMLERİNİN İN VİTRO REAKTİVASYON POTENSİ

2003 yılında, K027 ve K048 adlı iki yeni ümit verici asetilkolinesteraz reaktivatörü AChE; EC 3.1.1.7 geliştirilmiştir. Her ikisi de HI-6 ve trimedoxime TMB-4 türevleri olarak tasarlanmıştır. Bunlar birinci piridinhalkasında dördüncü pozisyonda bir oksim grubu, ikinci piridin halkasında dördüncü pozisyonda bir karbomil grubuolmak üzere iki kuarterner piridin halkası içermekte ve sadece iki piridin halkası arasındaki bağlantı halkasınınuzunluğu bakımından farklılık göstermektedirler K027 – üç metilen köprüsü, K048 – dört metilen köprüsü . Buçalışmada, söz konusu reaktivatörlerin sinir gazı tabun GA ile inhibe edilen AchE’ı in vitroolarak tekraraktifleştirme güçleri gösterilmek istenmiştir. Uygun enzim kaynağı olarak sıçan ve insan beyni kolinesterazlarıkullanılmıştır. Bu bulguya dayanarak insanlarla ilgili reaktivasyon testlerinin AChE reaktivite gelişim yöntemlerini deiçermesi gerektiği düşünülmektedir

Anahtar Kelimeler:

Asetilkolinesteraz reaktivatör, asetilkolinesteraz reaktivatör I (K027), asetilkolinesterazreaktivatör II (K048), tabun

IN VITRO REACTIVATION POTENCY OF NEWLY DEVELOPED OXIMES K027 AND K048

In 2003, we have developed two promising acetylcholinesterase AChE; EC 3.1.1.7 reactivators – K027 andK048. Both of them were designed as derivatives of HI-6 and trimedoxime TMB-4 . They consist of two quaternarypyridinium rings, one oxime group in the position four at the first pyridinium ring, one carbamoyl group at theposition four at the second pyridinium ring and they differ just in the length of the connection chain between bothpyridinium rings K027 – three-methylene bridge, K048 – four-methylene bridge . In our study, we would like to showtheir potency to reactivate in vitroAChE inhibited by nerve agent tabun GA . We have used rat and human braincholinesterases as the appropriate source of the enzyme. As resulted from this work, there are differences in thecourse of the reactivation process between rat and human species. Owing to this fact, reactivation test with humanspecies should be included in the AChE reactivator developmental process

Keywords:

Acetylcholinesterase reactivator, acetylcholinesterase reactivator I (K027), acetylcholinesterasereactivator II (K048), tabun,

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