Design, synthesis and evaluation of novel nonquaternary and 3 non-oxime reactivators for acetylcholinesterase inhibited by organophosphates.
Acetylcholinesterase
/ metabolism
Cholinesterase Inhibitors
/ toxicity
Cholinesterase Reactivators
/ chemical synthesis
Drug Design
Humans
Kinetics
Molecular Docking Simulation
Nerve Agents
/ toxicity
Organophosphates
/ toxicity
Oximes
/ chemical synthesis
Pesticides
/ toxicity
Piperazine
/ analogs & derivatives
Nerve agent
Non-oxime
Nonquaternary
Pesticide
Reactivator
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
17
10
2019
revised:
28
04
2020
accepted:
29
04
2020
pubmed:
11
5
2020
medline:
4
3
2021
entrez:
11
5
2020
Statut:
ppublish
Résumé
A new series of novel nonquaternary conjugates and non-oxime reactivators for reactivation of both nerve agents and pesticides inhibited hAChE were described in this paper. Conjugates with piperazine linked to the substituted salicylaldoxime emerged as efficient reactivators for VX inhibited hAChE. The in vitro reactivation experiment showed that some of them were equal or more efficient reactivators for pesticides inhibited hAChE than obidoxime. It was also found that some non-oxime derivatives of Mannich phenols displayed obvious reactivation potency for VX, sarin and pesticides inhibited hAChE even in very low concentration. It has been proved that introduction of peripheral site ligands with widespread aromatic system and amide substitutions could increase binding affinity for inhibited hAChE in most cases, which contribute to the reactivation efficiency.
Identifiants
pubmed: 32388435
pii: S0045-2068(19)31751-1
doi: 10.1016/j.bioorg.2020.103902
pii:
doi:
Substances chimiques
Cholinesterase Inhibitors
0
Cholinesterase Reactivators
0
Nerve Agents
0
Organophosphates
0
Oximes
0
Pesticides
0
Piperazine
1RTM4PAL0V
salicylaldoxime
2QTV2A0T5Q
Acetylcholinesterase
EC 3.1.1.7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
103902Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declared that there is no conflict of interest.