Naslov
New Uncharged 2-Thienostilbenes Oximes as Reactivators of cholinesterases

Autori
Mlakić, Milena ; Čadež, Tena ; Barić, Danijela ; Kovarik, Zrinka ; Škorić, Irena

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

Izvornik
XIV. susret mladih kemijskih inženjera : knjiga sažetaka = XIV Meeting of Young Chemical Engineers : Book of Abstracts / Žižek, Krunoslav ; Katančić, Zvonimir ; Kovačić, Marin - Zagreb : Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI), 2022, 126-126

Skup
XIV. susret mladih kemijskih inženjera (SMLKI 2022)

Mjesto i datum
Zagreb, Hrvatska, 24.02.2022. - 25.02.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
AChE ; BChE ; reactivation ; heterostilbenes ; spectroscopy ; docking

Sažetak
Oximes, the symptomatic drugs currently were used as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the treatment of neurological disorders such as Alzheimer’s and Parkinson’s disease. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by organophosphates (OPs) as nerve agents and pesticides compromises normal cholinergic nerve signal transduction in the peripheral and central nervous systems (CNS) leading to cholinergic crisis. The treatment comprises an antimuscarinic drug and an oxime reactivator of the inhibited enzyme. Oximes in use have quaternary nitrogens, and therefore poorly cross the brain–blood barrier. In this work, we synthesized novel uncharged thienostilbene oximes by sequence of three reactions in very high yields. Eight trans, anti- and trans, syn-isomers of oximes were tested as reactivators of nerve-agent- inhibited AChE and BChE. Four derivatives reactivated cyclosarin-inhibited BChE up to 70% in two hours of reactivation, and docking studies confirmed their productive interactions with the active site of cyclosarin-inhibited BChE. Based on the moderate binding affinity of both AChE and BChE for all selected oximes, these compounds present a new class of oximes with the potential for further development of CNS-active therapeutics in OP poisoning.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Kemijsko inženjerstvo

POVEZANOST RADA