Reactivation Potential of Novel More Lipophilic Pralidoxime Analogs

Author(s): Martina Hrabinova, Jan Misik, Daniel Jun, Kamil Kuca*.

Journal Name: Letters in Drug Design & Discovery

Volume 15 , Issue 8 , 2018

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Graphical Abstract:


Background: Novel, more lipophilic analogs of pralidoxime - 2-PAM (K347, K087) and 4-PAM (K349, K120) have been tested in this study due to the recently discovered fact that monoquaternary AChE reactivators penetrate BBB in higher amount. In vitro tests were run against the several organophosphorus agents including tabun, sarin, cyclosarin, soman, VX-agent, Russian VX-agent, diisopropylfluorophosphate and chlorpyrifos.

Methods: Standard potentiometric method was used for the evaluation of reactivation efficacy. Rat brain homogenate was used as the source of acetylcholinesterase.

Results: The efficacy of novel reactivators was compared against standard AChE reactivators (2- PAM and 4-PAM). K349 and K120 (10-3 M) were 1.1 and 4.8-fold more effective in the reactivation of sarin-inhibited AChE compared with 4-PAM, respectively. Moreover, K120 in 10- 5 M concentration, which is attainable in the plasma within antidotal treatment of intoxication, was 2.1-fold more effective than standard. Generally, the best results were observed for oxime K120.

Conclusion: None of the newly prepared benzylated 2-PAM and 4-PAM analogs showed such a broad spectrum of action as standard pralidoxime.

Keywords: Acetylcholinesterase, antidotes, reactivator, nerve agent, potentiometric method, blood brain barrier.

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Article Details

Year: 2018
Page: [822 - 827]
Pages: 6
DOI: 10.2174/1570180814666171013163019
Price: $65

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