Citation

Habiballah S, Chambers J, Meek E, Reisfeld B. J. Comput. Aided Mol. Des. 2023; ePub(ePub): ePub.

Copyright

(Copyright © 2023, Holtzbrinck Springer Nature Publishing Group)

DOI

10.1007/s10822-023-00537-x

PMID

37796381

Abstract

Owing to their potential to cause serious adverse health effects, significant efforts have been made to develop antidotes for organophosphate (OP) anticholinesterases, such as nerve agents. To be optimally effective, antidotes must not only reactivate inhibited target enzymes, but also have the ability to cross the blood-brain barrier (BBB). Progress has been made toward brain-penetrating acetylcholinesterase reactivators through the development of a new group of substituted phenoxyalkyl pyridinium oximes. To help in the selection and prioritization of compounds for future synthesis and testing within this class of chemicals, and to identify candidate broad-spectrum molecules, an in silico framework was developed to systematically generate structures and screen them for reactivation efficacy and BBB penetration potential.

Language: en

Keywords

Machine learning; Organophosphate; Antidote; Blood–brain barrier; Oxime; QSAR; Virtual screening