Binder J

General

Full name : Binder Jiri

First name : Jiri

Mail : Department of Pharmaceutical Chemistry and Drug Control\; Faculty of Pharmacy in Hradec Kralove\; Charles University in Prague\; 50005 Hradec Kralove

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Country : Czech Republic

Email : jiribinder@seznam.cz

Phone : +420776000279

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References (3)

Title : Pseudo-catalytic scavenging: searching for a suitable reactivator of phosphorylated butyrylcholinesterase - Kovarik_2010_Chem.Biol.Interact_187_167
Author(s) : Kovarik Z , Katalinic M , Sinko G , Binder J , Holas O , Jung YS , Musilova L , Jun D , Kuca K
Ref : Chemico-Biological Interactions , 187 :167 , 2010
Abstract : Butyrylcholinesterase is considered to be an endogenous stoichiometric bioscavenger of organophosphorus compounds (OPs), but due to limited concentration of BChE in the organism, stoichiometric reduction of OP is not always sufficient. This can be improved by creating a pseudo-catalytic scavenger adding oximes as reactivators of inhibited exogenous BChE. In order to improve the BChE bioscavenging function in tabun or paraoxon poisoning, we tested in vitro reactivation of phosphorylated human plasma BChE by bispyridinium oximes varying in the length and type of the linker between rings, and in the position of the oxime group on the ring. Among the tested oximes, the most potent reactivators of tabun-inhibited BChE were K117 [1,1'-(2,2'-oxybis(ethane-2,1-diyl))bis(4-hydroxyiminomethyl pyridinium) bromide] and K127 [4-carbamoyl-1-(2-(2-(4-(hydroxyiminomethyl) pyridinium-1-yl)ethoxy)ethyl)pyridinium bromide]. Reactivation by these oximes (1mM) reached about 50% of control activity after only 20 min; however, reactivation stopped at 70%. Reactivation of paraoxon-inhibited BChE by all of the selected oximes was slow. Using molecular mechanics, we performed docking of the oximes to tabun-inhibited BChE in order to discuss possible structural modifications of bispyridinium oximes to improve reactivation of phosphorylated BChE.
ESTHER : Kovarik_2010_Chem.Biol.Interact_187_167
PubMedSearch : Kovarik_2010_Chem.Biol.Interact_187_167
PubMedID: 20206154

Title : Synthesis and in vitro evaluation of N-alkyl-7-methoxytacrine hydrochlorides as potential cholinesterase inhibitors in Alzheimer disease - Korabecny_2010_Bioorg.Med.Chem.Lett_20_6093
Author(s) : Korabecny J , Musilek K , Holas O , Binder J , Zemek F , Marek J , Pohanka M , Opletalova V , Dohnal V , Kuca K
Ref : Bioorganic & Medicinal Chemistry Lett , 20 :6093 , 2010
Abstract : All approved drugs for Alzheimer disease (AD) in clinical practice ameliorate the symptoms of the disease. Among them, acetylcholinesterase inhibitors (AChEIs) are used to increase the cholinergic activity. Among new AChEI, tacrine compounds were found to be more toxic compared to 7-MEOTA (9-amino-7-methoxy-1,2,3,4-tetrahydroacridine). In this Letter, series of 7-MEOTA analogues (N-alkyl-7-methoxytacrine) were synthesized. Their inhibitory ability was evaluated on recombinant human acetylcholinesterase (AChE) and plasmatic human butyrylcholinesterase (BChE). Three novel compounds showed promising results towards hAChE better to THA or 7-MEOTA. Three compounds resulted as potent inhibitors of hBChE. The SAR findings highlighted the C(6)-C(7)N-alkyl chains for cholinesterase inhibition.
ESTHER : Korabecny_2010_Bioorg.Med.Chem.Lett_20_6093
PubMedSearch : Korabecny_2010_Bioorg.Med.Chem.Lett_20_6093
PubMedID: 20817518

Title : Interaction of nerve agent antidotes with cholinergic systems - Soukup_2010_Curr.Med.Chem_17_1708
Author(s) : Soukup O , Tobin G , Kumar UK , Binder J , Proska J , Jun D , Fusek J , Kuca K
Ref : Curr Med Chem , 17 :1708 , 2010
Abstract : The poisoning with organophosphorus compounds represents a life threatening danger especially in the time of terroristic menace. No universal antidote has been developed yet and other therapeutic approaches not related to reactivation of acetylcholinesterase are being investigated. This review describes the main features of the cholinergic system, cholinergic receptors, cholinesterases and their inhibitors. It also focuses on the organophosphorus nerve agents, their properties, effects and a large part describes various possibilities in treatments, mainly traditional oxime therapies based on reactivation of AChE. Furthermore, non-cholinesterase coupled antidotal effects of the oximes are thoroughly discussed. These antidotal effects principally include oxime interactions with muscarinic and nicotinic receptors.
ESTHER : Soukup_2010_Curr.Med.Chem_17_1708
PubMedSearch : Soukup_2010_Curr.Med.Chem_17_1708
PubMedID: 20345348