Isatin–pyridine oxime hybrids as potential reactivators of A-242-inhibited acetylcholinesterase

Three new isatin-pyridine-2-oxime hybrids (AM01-03) were synthesized and experimentally evaluated as reactivators of acetylcholinesterase (AChE) inhibited by a surrogate of the nerve agent A-242, in comparison with their 4-oxime isomers previously reported by our research group. Furthermore, the interactions of these molecules within the AChE/A-242 complex were assessed through docking and molecular dynamics (MD) simulations. Our results show that the 2-oxime isomers, unlike their 4-oxime analogues, can reactivate AChE inhibited by the A-242 surrogate at 100 µM and are even capable of outperforming the commercial reactivator HI-6. These findings suggest that isatin-oxime hybrids may exhibit a specific biological activity-similar to that observed for obidoxime and trimedoxime-in the reactivation of AChE inhibited by A-242.

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Publication Details

Journal
Archives of Toxicology
Published
2026-05-22
DOI
https://doi.org/10.1007/s00204-026-04449-1
Primary Topic
Cholinesterase and Neurodegenerative Diseases
Type
article
Field-Weighted Citation Impact
0.00

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article

Isatin–pyridine oxime hybrids as potential reactivators of A-242-inhibited acetylcholinesterase

Dipanjan Bhattacharyya, Steven R. LaPlante, Pat Forgione, M A L da Silva et al.
Archives of Toxicology
Cholinesterase and Neurodegenerative Diseases
article

Isatin–pyridine oxime hybrids as potential reactivators of A-242-inhibited acetylcholinesterase

Dipanjan Bhattacharyya, Steven R. LaPlante, Pat Forgione, M A L da Silva, Tanos C. C. França, Marcelo Santos, Amanda M. V. Pinto, Samir F. de A. Cavalcante, Daniel A. S. Kitagawa, Salim T. Islam, Joyce S. F. Diz
article en

Abstract

Three new isatin-pyridine-2-oxime hybrids (AM01-03) were synthesized and experimentally evaluated as reactivators of acetylcholinesterase (AChE) inhibited by a surrogate of the nerve agent A-242, in comparison with their 4-oxime isomers previously reported by our research group. Furthermore, the interactions of these molecules within the AChE/A-242 complex were assessed through docking and molecular dynamics (MD) simulations. Our results show that the 2-oxime isomers, unlike their 4-oxime analogues, can reactivate AChE inhibited by the A-242 surrogate at 100 µM and are even capable of outperforming the commercial reactivator HI-6. These findings suggest that isatin-oxime hybrids may exhibit a specific biological activity-similar to that observed for obidoxime and trimedoxime-in the reactivation of AChE inhibited by A-242.

Archives of Toxicology
Defense Information School (US), Institut National de la Recherche Scientifique (CA), Military Institute of Engineering (BR), PROTEO (CA), Nuclear Engineering Institute (BR), National Water Agency (BR), Concordia University (CA), University of Hradec Králové (CZ)
Conselho Nacional de Desenvolvimento Científico e Tecnológico, Organisation for the Prohibition of Chemical Weapons, Universidade Federal do Rio de Janeiro, Instituto Militar de Engenharia
Openalex Percentile: Top 7%
Cholinesterase and Neurodegenerative Diseases
DOIOpen Access PDFOpenAlex
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