The series of symmetrical and unsymmetrical isoquinolinium-5-carbaldoximes was designed and prepared for cholinesterase reactivation purposes. The novel compounds were evaluated for intrinsic acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) inhibition, when the majority of novel compounds resulted with high inhibition of both enzymes and only weak inhibitors were selected for reactivation experiments on human AChE or BChE inhibited by sarin, VX, or paraoxon. The AChE reactivation for all used organophosphates was found negligible if compared to the reactivation ability of obidoxime. Importantly, two compounds were found to reactivate BChE inhibited by sarin or VX better to obidoxime at human attainable concentration. One compound resulted as better reactivator of NEMP (VX surrogate)-inhibited BChE than obidoxime. The in vitro results were further rationalized by molecular docking studies showing future directions on designing potent BChE reactivators.

• Keywords
• Acetylcholinesterase, butyrylcholinesterase, organophosphate, oxime, reactivator,
• MeSH
• Acetylcholinesterase drug effects   MeSH
• Butyrylcholinesterase drug effects   MeSH
• Cholinesterase Inhibitors pharmacology   MeSH
• Isoquinolines chemical synthesis   chemistry   pharmacology   MeSH
• Humans MeSH
• Cholinesterase Reactivators pharmacology   MeSH
• Molecular Docking Simulation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Acetylcholinesterase MeSH
• Butyrylcholinesterase MeSH
• Cholinesterase Inhibitors MeSH
• Isoquinolines MeSH
• Cholinesterase Reactivators MeSH