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Published on: November 23, 2016
Isatin-pyridine oxime hybrids as potential reactivators of A-242-inhibited acetylcholinesterase
Amanda M V Pinto1,2, Dipanjan Bhattacharyya2,3,4, Munique C J da Silva1,5
1Laboratory of Molecular Modeling Applied to Chemical and Biological Defense, Military Institute of Engineering, Rio de Janeiro, 22290-270, RJ, Brazil.
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.
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