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Čadež T, Kolić D, Šinko G, et al. Assessment of four organophosphorus pesticides as inhibitors of human acetylcholinesterase and butyrylcholinesterase. Sci Rep. 2021;11(1):21486doi: 10.1038/s41598-021-00953-9.
Čadež, T., Kolić, D., Šinko, G., & Kovarik, Z. (2021). Assessment of four organophosphorus pesticides as inhibitors of human acetylcholinesterase and butyrylcholinesterase. Scientific reports, 11(1), 21486. https://doi.org/10.1038/s41598-021-00953-9
Čadež, Tena, et al. "Assessment of four organophosphorus pesticides as inhibitors of human acetylcholinesterase and butyrylcholinesterase." Scientific reports vol. 11,1 (2021): 21486. doi: https://doi.org/10.1038/s41598-021-00953-9
Čadež T, Kolić D, Šinko G, Kovarik Z. Assessment of four organophosphorus pesticides as inhibitors of human acetylcholinesterase and butyrylcholinesterase. Sci Rep. 2021 Nov 02;11(1):21486. doi: 10.1038/s41598-021-00953-9. PMID: 34728713; PMCID: PMC8563940.
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Sci Rep. 2021 Nov 02;11(1):21486. doi: 10.1038/s41598-021-00953-9.

Assessment of four organophosphorus pesticides as inhibitors of human acetylcholinesterase and butyrylcholinesterase.

Scientific reports

Tena Čadež, Dora Kolić, Goran Šinko, Zrinka Kovarik

Affiliations

  1. Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10 000, Zagreb, Croatia.
  2. Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10 000, Zagreb, Croatia. [email protected].

PMID: 34728713 PMCID: PMC8563940 DOI: 10.1038/s41598-021-00953-9

Abstract

Toxicity of organophosphorus compounds (OPs) remains a major public health concern due to their widespread use as pesticides and the existence of nerve agents. Their common mechanism of action involves inhibition of enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which are crucial for neurotransmission. Both chronic and acute poisoning by OPs can leave long-lasting health effects even when the patients are treated with standard medical therapy. Therefore, an increasing urgency exists to find more effective oxime reactivators for compounds which are resistant to reactivation, especially phosphoramidates. Here, we investigated in silico and in vitro interactions and kinetics of inhibition for human cholinesterases with four organophosphate pesticides-ethoprophos, fenamiphos, methamidophos and phosalone. Overall, ethoprophos and fenamiphos displayed higher potency as inhibitors for tested cholinesterases. Our results show that methamidophos-inhibited hAChE was more susceptible to reactivation than hAChE inhibited by fenamiphos by selected oximes. Molecular modelling enabled an evaluation of interactions important for specificity and selectivity of both inhibition and reactivation of cholinesterases. Two newly developed reactivators-bispyridinium triazole oxime 14A and zwitterionic oxime RS194B possess remarkable potential for further development of antidotes directed against pesticides and related phosphoramidate exposures, such as nerve agents tabun or Novichoks.

© 2021. The Author(s).

References

  1. J Biol Chem. 2020 Mar 27;295(13):4079-4092 - PubMed
  2. J Am Chem Soc. 2008 Nov 26;130(47):16011-20 - PubMed
  3. FEBS Lett. 2006 May 29;580(13):3167-72 - PubMed
  4. Biochemistry. 2004 Mar 23;43(11):3222-9 - PubMed
  5. Biochem Pharmacol. 1989 Feb 15;38(4):633-40 - PubMed
  6. Neurotoxicology. 2020 Sep;80:60-70 - PubMed
  7. Neurotoxicology. 2009 Sep;30(5):772-6 - PubMed
  8. Toxicology. 2019 Mar 1;415:56-69 - PubMed
  9. Biochem J. 2020 Aug 14;477(15):2771-2790 - PubMed
  10. Arch Biochem Biophys. 2013 Jan 15;529(2):140-5 - PubMed
  11. J Pharmacol Exp Ther. 2021 Sep;378(3):315-321 - PubMed
  12. J Med Chem. 2012 Aug 9;55(15):6716-23 - PubMed
  13. Chem Biol Interact. 2013 Mar 25;203(1):77-80 - PubMed
  14. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Sep 1;63(Pt 9):723-7 - PubMed
  15. Toxicol Lett. 2020 Mar 15;321:83-89 - PubMed
  16. J Pharmacol Exp Ther. 2018 Nov;367(2):363-372 - PubMed
  17. Toxicology. 2012 Feb 26;292(2-3):145-50 - PubMed
  18. J Biol Chem. 2011 Aug 26;286(34):29718-24 - PubMed
  19. Toxicol Lett. 2018 Sep 1;293:229-234 - PubMed
  20. J Biol Chem. 2012 Apr 6;287(15):11798-809 - PubMed
  21. Biochem Pharmacol. 2010 Feb 1;79(3):507-15 - PubMed
  22. J Genet. 2017 Mar;96(1):187-201 - PubMed
  23. Environ Toxicol Pharmacol. 2005 May;19(3):433-46 - PubMed
  24. Arh Hig Rada Toksikol. 2020 Jun 29;71(2):163-166 - PubMed
  25. Toxicology. 2006 Feb 15;219(1-3):85-96 - PubMed
  26. Neurobiol Dis. 2020 Jan;133:104406 - PubMed
  27. Chem Biol Interact. 1999 May 14;119-120:61-9 - PubMed
  28. J Neurochem. 2021 Sep;158(6):1217-1222 - PubMed
  29. Toxicology. 2019 Feb 1;413:13-23 - PubMed
  30. Arh Hig Rada Toksikol. 2009 Mar;60(1):19-26 - PubMed
  31. EXCLI J. 2018 Nov 08;17:1101-1136 - PubMed
  32. Biochem Pharmacol. 2007 Jun 1;73(11):1807-17 - PubMed
  33. Biochim Biophys Acta. 1999 Aug 17;1433(1-2):261-71 - PubMed
  34. Ther Drug Monit. 2002 Feb;24(1):144-9 - PubMed
  35. Arch Environ Health. 1990 May-Jun;45(3):180-4 - PubMed
  36. Arh Hig Rada Toksikol. 2020 Dec 31;71(4):266-284 - PubMed
  37. Acta Neuropathol. 2019 Sep;138(3):343-362 - PubMed
  38. Sci Rep. 2019 Jul 19;9(1):10530 - PubMed
  39. Biochem Pharmacol. 1961 Jul;7:88-95 - PubMed
  40. Intern Med. 2007;46(13):965-9 - PubMed
  41. Biochemistry. 2006 Jan 10;45(1):74-81 - PubMed
  42. Arh Hig Rada Toksikol. 2007 Jun;58(2):201-9 - PubMed
  43. Molecules. 2017 Nov 29;22(12): - PubMed
  44. Arch Toxicol. 2012 Sep;86(9):1379-86 - PubMed
  45. Chemistry. 2019 Mar 15;25(16):4100-4114 - PubMed
  46. J Toxicol Clin Toxicol. 2001;39(4):333-6 - PubMed
  47. Chem Biol Interact. 2016 Nov 25;259(Pt B):122-132 - PubMed
  48. Ecotoxicol Environ Saf. 1991 Dec;22(3):337-44 - PubMed

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