Design and Docking Study of Novel Oximes as Reactivators of Inhibited Acetylcholinesterase with Nerve Agents

In this study, a group of nitron-based oximes involving a pyridinium moiety were assessed as novel drug candidates in the reactivation of inhibited AChE in a docking study.
The chemical structures of novel reactivators were built using the HyperChem program and conformational studies were performed using a semi-experimental method. Docking calculations on all of the designed oximes were carried out using the Auto Dock program.
The recorded binding energy for obidoxime and 2-PAM were -8.59 and -5.61 respectively. These current oxime-formed hydrogen bond and π-π interactions in the active site. Docking calculations showed that new nitrone-based oximes formed hydrogen bonds and π-π interactions with peripheral anionic, aromatic and catalytic triad residues in the active site. Also, all of the new compounds possess better binding energies than 2-PAM and were comparable with obidoxime.
The results showed that all of the new oximes possess promising binding energies compared with the standard oximes of 2-PAM and obidoxime. Bis-pyridinum oximes have better results than mono-pyridinum oximes caused by the presence of additional pi-pi and hydrogen bonding interactions. In most cases, the designed oximes where the imidazole ring was positioned at position 3 have better orientation and more favorable interactions in active site.