Jiří Cabal

Synthesis of a new reactivator of tabun-inhibited acetylcholinesterase

Synthesis of a new asymmetric bisquaternary reactivator of tabun-inhibited acetylcholinesterase-1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide is described. Reactivation potency of this oxime is compared to the currently used reactivators-pralidoxime, obidoxime and H-oxime HI-6.

Synthesis of a potential reactivator of acetylcholinesterase-1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium)- propane dibromide

Two methods for the synthesis of a new unsymmetric bispyridinium oxime-1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium)propane dibromide are described. In vitro efficacy of this new oxime to reactivate sarin-inhibited acetylcholinesterase has been evaluated.

A comparison of the efficacy of a new asymmetric bispyridinium oxime BI-6 with currently available oximes and H oximes against soman by in vitro and in vivo methods

The reactivating and therapeutic efficacy of a new acetylcholinesterase reactivator, designated BI-6(1-/2-hydroxyiminomethylpyridinium/-4-/carbamoylpyridinium+ ++/-2-butene dibromide), against the organophosphate soman was compared with oximes at present used (pralidoxime, obidoxime, methoxime) and H oximes (HI-6, HLö-7) using in vitro and in vivo methods. H oximes HI-6 and HLö-7 seem to be the most efficacious acetylcholinesterase reactivators against soman according to the evaluation of their reactivating and therapeutic efficacy in vitro as well as in vivo. The new oxime BI-6 is not as effective as the H oximes against soman, nevertheless it is significantly more effective against soman than the currently available oximes, pralidoxime, obidoxime and methoxime, which failed to protect rats poisoned with supralethal doses of soman. Our results confirm that the reactivating efficacy of oximes evaluated by the methods in vitro closely correlates not only with the potency of oximes in vivo in reactivating soman-inhibited acetylcholinesterase but also with the ability to protect rats poisoned with supralethal doses of soman.

A comparison of the efficacy of a new asymmetric bispyridinium oxime BI-6 with presently used oximes and H oximes against sarin by in vitro and in vivo methods

1 The reactivating and therapeutic efficacy of a new acetylcholinesterase reactivator, designated BI-6 (1-/2-hydroxyiminomethylpyridinium/-4-/carbamoylpyridinium/-2-butene dibromide), against organophosphate sarin was compared with presently used oximes (pralidoxime, obidoxime, methoxime) and H oximes (HI-6, HLö-7) by in vitro and in vivo methods. 2 Our results confirm that the new oxime BI-6 is a significantly more efficacious acetylcholinesterase reactivator than currently available pralidoxime and obidoxime but not as effective as H oximes (HI-6, HLö-7) in vitro as well as in vivo. In addition, the oxime BI-6 is able to protect supralethal sarin poisoned rats at human-relevant doses. 3 Our data also suggest that the potency of oximes tested to reactivate sarin-inhibited acetylcholinesterase in vitro closely corresponds to their reactivating efficacy in vivo and their ability to protect rats poisoned with supralethal doses of sarin.

Evaluation of Newly Synthesized Reactivators of the Brain Cholinesterase Inhibited by Sarin Nerve Agent

In this work in vitro evaluation of the reactivation potency of the newly synthesized reactivators for acetylcholinesterase (AChE; EC 3.1.1.7) is described. Using this method, reactivation potency of 21 potential reactivators of AChE inhibited by the nerve agent sarin has been evaluated. We have confirmed the fact that currently the most promising AChE reactivator, HI-6, is the most effective reactivator of sarin-inhibited AChE. There are only three AChE reactivators—HI-6, TO033 and TO047—able to satisfactorily reactivate sarin-inhibited AChE at the concentration 10−5 M, which is nontoxic for human use. On the other hand, there are 14 AChE reactivators, that are able to reactivate sarin-inhibited AChE at the concentration 10−3 M. However, this concentration of reactivator is probably toxic for human use.

Determination of Benzalkonium Bromide Homologues in Disinfection Products Using High‐Performance Liquid Chromatography

Abstract In this work, the two rapid reversed‐phase high‐performance liquid chromatographic (RP‐HPLC) methods were developed for the determination of seven homologues of benzalkonium bromide in hospital disinfectants. The first one uses column Purospher RP‐18e and mixture of methanol‐acetic acid and lithium perchlorate‐octanesulphonic acid aqueous solution as a mobile phase; the second method is performed on Waters Spherisorb Cyano column, and mobile phase consists of acetonitrile‐acetate buffer. Both techniques use UV detection at 263 nm. The time of analysis is shorter than 15 min, and limits of detection are bellow 0.005 mg/mL. The methods were successfully applied for analysis of three commercial disinfectants. Supported by grant of Ministry of Industry and Trade (Czech Republic) FF‐P2/115. The authors thank Mrs. Martina Hrabinová for her technical help.