https://orcid.org/0000-0001-6693-6061
Abstract
Aim: Organophosphorus compounds are irreversible inhibitors of AChE. Without immediate countermeasure, intoxication leads quickly to death. None of the clinically-used causal antidotes can ensure a good prognosis for any poisoned patient. When fallen into the wrong hands, organophosphates represent a serious threat to mankind. Results & methodology: Herein, we describe two novel compounds as unique merged molecules built on a tacrine scaffold against organophosphorus intoxication. These reactivators of AChE have balanced physicochemical properties, and should be able to cross the blood–brain barrier with a slightly lowered cytotoxicity profile compared to reference tacrine. Conclusion: Their efficiency compared with pralidoxime and obidoxime was proved against dichlorvos.
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Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184
Acknowledgments
Computational resources were provided by the CESNET LM2015042 and the CERIT Scientific Cloud LM2015085, provided under the programme ‘Projects of Large Research, Development, and Innovations Infrastructures’. The authors are grateful to I McColl for assistance with the manuscript.
Financial & competing interests disclosure
The work was supported by the grant of the by Ministry of Health of the Czech Republic, grant number 17-32801A, by the Faculty of Military Health Sciences (Long-term development plan and student project SV/FVZ201601), and by MH CZ - DRO (University Hospital Hradec Kralove, no. 00179906). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.