Current study on the development of bis-pyridinium oxime reactivators for the antidotal treatment of poisoning by toxic organophosphorus agents

Current Organic Chemistry

Volumn 15, Issue 3, 2011, Pages 433-444

  Jung, Young Sik ^a   Kuca, Kamil ^b  

^a Korea Research Institute of Chemical Technology   (South Korea)

^b UNIVERSITY OF DEFENCE   (Czech Republic)

Author keywords

Acetylcholinesterase; Bis pyridinium oximes; Blood brain barrier; Nerve agents; Oxim reactivator; Pesticide

Indexed keywords

'CURRENT; ACETYLCHOLINESTERASE; ACETYLCHOLINESTERASE INHIBITION; BIS-PYRIDINIA OXIME; BLOOD-BRAIN BARRIER; BROAD SPECTRUM; NERVE AGENTS; OXIM REACTIVATOR; PYRIDINIUM; SYNTHESISED;

BLOOD;

EID: 78650930456     PISSN: 13852728     EISSN: None     Source Type: Journal    
DOI: 10.2174/138527211794072579     Document Type: Review

References (20)

1. th ed. (McGraw Hill, New York), 1996, pp. 175-191.
2. Marrs, T.C. Organophosphate poisoning. Pharmacol. Ther. 1993, 58, 51-66.
3. Wilson, I.B. Acetylcholinesterase: XI. Reversibility of tetraethyl pyrophos-phate inhibition. J. Biol. Chem. 1951, 190, 111-117.
4. Wilson, I.B.; Ginsburg, S. Reactivation of acetylcholinesterase inhibited by alkylphosphates. Arch. Biochem. 1955, 54, 569-571.
5. Musilek, K.; Holas, O.; Jun, D.; Dohnal, V.; Gunn-Moore, F.; Opletalova, V.; Dolezal, M.; Kuca, K. Monooxime reactivators of acetylcholinesterase with (E)-but-2-ene linker: Preparation and reactivation of tabun- and paraoxon-inhibited acetylcholinesterase. Bioorg. Med. Chem. 2007, 15, 6733-6741.
6. Kuca, K.; Jun, D.; Musilek, K. Structural requirements of acetylcho-linesterase reactivators. Mini-Rev. Med. Chem. 2006, 6, 269-277.
7. Musilek, K.; Jun, D.; Cabal, J.; Kassa, J.; Gunn-Moore, F.; Kuca, K. Design of a potent reactivator of tabun-inhibited acetylcholinesterase-synthesis and evaluation of (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203). J. Med. Chem. 2007, 50, 5514-5518.
8. Kim, T.H.; Kuca, K.; Jun, D.; Jung, Y.S. Design and synthesis of new bispyridinium oxime reactivators for acetyleholinesterase inhibited by organo-phosphorous nerve agents. Bioorg. Med. Chem. Lett. 2005, 15, 2914.
9. Kuca, K.; Bielavsky, J.; Cabal, J.; Bielavska, M. Synthesis of a potential reactivator of acetylcholinesterase-1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium)propane dibromide. Tetrahedron Lett. 2003, 44, 3123-3125.
10. Kim, T.H.; Oh, K.A.; Park, N.J.; Park, N.S.; Kim, Y.J.; Yum, E.K.; Jung, Y.S. Reactivation study of pyridinium oximes for acetylcholinesterases inhibited by paraoxon or DFP. J. Appl. Biomed. 2006, 4, 67-72.
11. Kuca, K.; Jun, D.; Kim, T.H.; Cabal, J.; Jung, Y.S. In vitro Evaluation of New Acetylcholinesterase Reactivators as Casual Antidotes against Tabun and Cyclosarin. Bull. Korean Chem. Soc. 2006, 27, 395-398.
12. Kassa, J.; Karasova, J.; Musilek, K.; Kuca, K.; Jung, Y.S. A Comparison of the Therapeutic and Reactivating Efficacy of Newly Developed Oximes (K117, K127) and Currently Available Oximes (Obidoxime, Trimedoxime, HI-6) in Tabun-Poisoned Rats and Mice. Drug Chem. Tox. 2008, 31, 371-381.
13. Karasova, J.Z.; Kassa, J.; Jung, Y.S.; Musilek, K.; Pohanka, M.; Kuca, K. Effect of Several New and Currently Available Oxime Cholinesterase Reactivators on Tabun-intoxicated Rats. Int. J. Mol. Sci. 2008, 9, 2243-2252.
14. Oh, K.A.; Yang, G.Y.; Jun, D.; Kuca, K.; Jung, Y.S. Bis-pyridiumaldoxime reactivators connected with CH2O(CH2)(n)OCH2 linkers between pyridinium rings and their reactivity against VX. Bioorg. Med. Chem. Lett. 2006, 16, 4852-4855.
15. Yang, G.Y.; Oh, K.A.; Park, N.J.; Jung, Y.S. New oxime reactivators connected with CH2O(CH2)nOCH2 linker and their reactivation potency for organophosphorus agents-inhibited acetylcholinesterase. Bioorg. Med. Chem. 2007, 15, 7704-7710.
16. Pang, Y.P.; Quiram, P.; Jelacic, T.; Hong, F.; Brimijoin, S. Highly potent, selective, and low cost bis-tetrahydroaminacrine inhibitors of acetylcho-linesterase. Steps toward novel drugs for treating Alzheimer's disease. J. Biol. Chem. 1996, 271, 23646-23649.
17. Pang, Y.P.; Perola, E.; Xu, K.; Prendergast, F.G. EUDOC: a computer program for identification of drug interaction sites in macromolecules and drug leads from chemical databases. J. Comput. Chem. 2001, 22, 1750-1771.
18. Oh, K.A.; Park, N.J.; Park, N.S.; Kuca, K.; Jun, D.; Jung, Y.S. Reactivation of DFP-and paraoxon-inhibited acetylcholinesterases by pyridinium oximes. Chem-Biol. Int. 2008, 175, 365-367.
19. Jeong, H.C.; Kang, N.S.; Park, N.J.; Yum, E.K.; Jung, Y.S. Reactivating potency of fluorinated pyridinium oximes for acetylcholinesterases inhibited by paraoxon organophosphorus agent. Bioorg. Med. Chem. Lett. 2009, 19, 1214-1217.
20. Jeong, H.C.; Park, N.J.; Chae, C.H.; Musilek, K.; Kassa, J.; Kuca, K.; Jung, Y.S. Fluorinated pyridinium oximes as potential reactivators for acetycholinesterases inhibited by paraoxon organophosphorus agent. Bioorg. Med. Chem. 2009, 17, 6213-6217.