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

Archives of Toxicology 2026 Open access

Read full text
Authors: Amanda M. V. Pinto, Dipanjan Bhattacharyya, M A L da Silva, Daniel A. S. Kitagawa, Marcelo C. Santos, Samir F. de A. Cavalcante, Salim T. Islam, Steven R. LaPlante, Pat Forgione, Joyce S. F. Diz, Tanos C. C. França
DOI: 10.1007/s00204-026-04449-1
Cited by: 1
References: 41

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.

Fields of Study & Subjects

Cholinesterase and Neurodegenerative Diseases Pesticide Exposure and Toxicity Enzyme function and inhibition

Publication details

Journal / source
Archives of Toxicology
Publisher
Springer Science and Business Media LLC
Volume
100
Issue
9
Pages
4077–4087
Publication date
22 May 2026
Language
EN